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Santoso LFAS, Kassis RA, Mohammed SK, Arora L, Emmanuel N, Nicolas G, Menendez JP. Adipose-derived stem cells in fat grafting for facial paralysis: A review of their therapeutic modality. JPRAS Open 2025; 44:145-161. [PMID: 40212106 PMCID: PMC11984942 DOI: 10.1016/j.jpra.2025.01.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2024] [Accepted: 01/25/2025] [Indexed: 04/13/2025] Open
Abstract
Facial paralysis, characterized by the complete loss of voluntary muscle control in the face, significantly affects individuals' daily lives. Recently, stem cell therapy has gained attention as a potential treatment for various medical conditions due to its capacity for self-renewal and differentiation into specialized cell types. Adipose-derived stem cells (ADSCs), obtained from the stromal-vascular fraction, consist of mesenchymal stem cells (MSCs), smooth muscle cells, endothelial cells, pericytes, lymphocytes, and tissue macrophages. Both differentiated and undifferentiated MSCs support axonal regeneration, enhance motor function, and promote growth factor release. ADSCs have been shown to improve regenerative outcomes, including better axonal development, increased myelinated fiber count, greater myelin thickness, and enhanced target reinnervation. These cells can differentiate into various lineages, particularly Schwann-like cells that facilitate axon regeneration. Additionally, ADSCs play a role in healing peripheral nerves by releasing neurotrophic and angiogenic factors. While the results are not as effective as nerve autografts, ADSCs offer an alternative option for reconstructing facial nerve paralysis.
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Affiliation(s)
| | - Raoul Al Kassis
- Department of General Medicine, Faculty of Medical Sciences, Lebanese University, Beirut, the Lebanonese Republic
| | - San Khasraw Mohammed
- Sulaymaniyah General Directorate of Health, Shar Hospital, Sulaymaniyah, Kurdistan Region 46001, Iraq
| | - Lakshay Arora
- University of Perpetual Help Jonelta Foundation School of Medicine, Las Piñas, Philippines
| | - Nancy Emmanuel
- Department of Dermatology, Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, São Paulo, Brazil
| | - Gregory Nicolas
- Department of Plastic and Reconstructive Surgery, Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, São Paulo, Brazil
| | - Juan Pablo Menendez
- Department of Plastic and Reconstructive Surgery, Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo, São Paulo, Brazil
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Rasekh M, Arshad MS, Ahmad Z. Advances in Drug Delivery Integrated with Regenerative Medicine: Innovations, Challenges, and Future Frontiers. Pharmaceutics 2025; 17:456. [PMID: 40284451 PMCID: PMC12030587 DOI: 10.3390/pharmaceutics17040456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2025] [Revised: 03/19/2025] [Accepted: 03/26/2025] [Indexed: 04/29/2025] Open
Abstract
Advances in drug delivery systems adapted with regenerative medicine have transformed healthcare by introducing innovative strategies to treat (and repair in many instances) disease-impacted regions of the human body. This review provides a comprehensive analysis of the latest developments and challenges in integrating drug delivery technologies with regenerative medicine. Recent advances in drug delivery technologies, including the design of biomaterials, localized delivery techniques, and controlled release systems guided by mathematical models, are explored to illustrate their role in enhancing therapeutic precision and efficacy. Additionally, regenerative medicine approaches are analyzed, with a focus on extracellular matrix components, stem cell-based therapies, and emerging strategies for organ regeneration in both soft and hard tissue and in vitro model engineering. In particular, the review also discusses the applications of cellular components, including stem cells, immune cells, endothelial cells, and specialized cells such as chondrocytes and osteoblasts, and highlights advancements in cell delivery methods and cell-cell interaction modulation. In addition, future directions and pivotal trends emphasizing the importance of interdisciplinary collaboration and cutting-edge innovations are provided to address successful therapeutic outcomes in regenerative medicine.
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Affiliation(s)
- Manoochehr Rasekh
- College of Engineering, Design and Physical Sciences, Brunel University of London, Uxbridge UB8 3PH, UK
| | | | - Zeeshan Ahmad
- Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH, UK
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Weir D, Wyles S, Behfar A, Eaton-Jankov L, Secic M, Bell M, Vyas K, Rohrich RJ. Human Platelet Extract (Plated) Hair Serum for Hair Health Improvement: A Double-blind, Placebo-controlled Clinical Study. PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN 2025; 13:e6562. [PMID: 40104384 PMCID: PMC11918706 DOI: 10.1097/gox.0000000000006562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 12/30/2024] [Indexed: 03/20/2025]
Abstract
Background The primary aim of this study was to demonstrate the benefits of topical human platelet exosome extract (HPE) (plated) hair serum for improving hair and scalp health in participants with self-perceived thinning hair. Methods This single-center, placebo-controlled, double-blind study enrolled 39 healthy men and women 18-65 years of age with self-perceived thinning hair. Participants applied either HPE for 9 months or a topical placebo for 6 months with the option to cross over to HPE at 6 months for an additional 3 months. End points included improvements in the global aesthetic appearance of hair, as assessed by a blinded live evaluator; participant-reported outcomes; hair trichoscopy; and independent physician photograph evaluations. Safety data included monitoring for adverse events. Results Blinded live evaluator assessments demonstrated statistically significant improvements in the global aesthetic appearance of hair for volume/fullness, density, scalp coverage, and appearance, with all P values less than 0.0001 within the HPE group and statistical improvement over the control at months 3 and 6 for volume/fullness, density, and scalp coverage. Participant-reported outcomes for within-group changes for HPE were statistically significant for all hair health parameters, including density, volume fullness, scalp coverage, scalp health, thickness, amount, quality, color, dryness, strength, and overall health of the hair. Hair trichoscopy analyses were significantly improved from baseline within the HPE group. Independent physician photography review demonstrated greater improvements within the HPE group. No adverse effects were observed. Conclusions This study demonstrates that topical HPE (plated) hair serum with Renewosome technology significantly improves hair and scalp health and is safe and well tolerated.
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Affiliation(s)
- David Weir
- From the Dallas Plastic Surgery Institute, Dallas, TX
| | | | | | | | | | | | - Krishna Vyas
- Division of Plastic and Reconstructive Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA
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Alvites R, Lopes B, Sousa AC, Pinheiro F, Silva E, Prada J, Varejão A, Maurício AC. Biomechanical Evaluation of the Sheep Common Peroneal Nerve After Crush Injury. Animals (Basel) 2025; 15:627. [PMID: 40075910 PMCID: PMC11898189 DOI: 10.3390/ani15050627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2025] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
Axonotmesis, a common peripheral nerve injury in humans and animals, leads to significant biomechanical and physiological consequences. The lack of a standardized crushing protocol for complex animal models limits research and therapeutic translations for humans and clinically relevant animal species. This study aimed to assess the impact of different crushing forces on the biomechanical behavior of the sheep common peroneal nerve and to establish a force for standardized in vivo protocols. Fourteen nerves of equal length were harvested and preserved and their initial diameter measured. They were subjected to crushing forces of 0 N, 80 N, and 180 N for one minute. Post crushing, the diameter, ultimate tensile strength, displacement at rupture, stress, strain, and stiffness were evaluated. Results showed that increasing crushing forces significantly affected nerve biomechanical parameters. Nerves crushed with 180N displayed lower tensile strength, displacement, and stiffness but higher stress and strain, indicating greater physical damage and structural degradation. These findings suggest that 180N induces substantial nerve fiber rupture and disruption of nerve trunk support elements, making it a candidate force for an axonotmesis protocol in the ovine model. Future in vivo studies should validate its effectiveness in creating complete crush injuries with functional and histological consequences, facilitating protocol standardization and translational research.
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Affiliation(s)
- Rui Alvites
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (B.L.); (A.C.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
- Instituto Universitário de Ciências da Saúde (IUCS), Cooperativa de Ensino Superior Politécnico e Universitário (CESPU), Avenida Central de Gandra 1317, 4585-116 Gandra PRD, Portugal
| | - Bruna Lopes
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (B.L.); (A.C.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
| | - Ana Catarina Sousa
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (B.L.); (A.C.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
| | - Fábio Pinheiro
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associated Laboratory for Energy, Transports and Aerospace (LAETA), Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), 4200-465 Porto, Portugal;
| | - Elisabete Silva
- Associated Laboratory for Energy, Transports and Aerospace (LAETA), Institute of Science and Innovation in Mechanical and Industrial Engineering (INEGI), 4200-465 Porto, Portugal;
| | - Justina Prada
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
- Centro de Ciência Animal e Veterinária (CECAV), Universidade de Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
- Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
| | - Artur Varejão
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
- Centro de Ciência Animal e Veterinária (CECAV), Universidade de Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
- Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5001-801 Vila Real, Portugal
- Neurology Service, Veterinary Hospital of the University of Trás-os-Montes e Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal
| | - Ana Colette Maurício
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal; (R.A.); (B.L.); (A.C.S.)
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, n° 228, 4050-313 Porto, Portugal;
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), 1300-477 Lisboa, Portugal; (J.P.); (A.V.)
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Yoon JY, Quang BD, Shin JS, Kim JB, Lee JH, Kim HW, Lee JH. Establishing Minimum Criteria for Stem Cells from Human Exfoliated Deciduous Teeth (SHEDs) Cultured in Human Platelet Lysate (hPL)-Contained Media as Cell Therapy Candidates: Characterization and Predictive Analysis of Secretome Effects. Cells 2025; 14:316. [PMID: 39996787 PMCID: PMC11854447 DOI: 10.3390/cells14040316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/14/2025] [Accepted: 02/18/2025] [Indexed: 02/26/2025] Open
Abstract
SHEDs have demonstrated significant potential in cell therapy due to their superior proliferation rate, self-renewal and differentiation capacity (particularly neurogenesis attributed to their neural crest origin), and the less invasive procedure required for tissue collection compared to other stem cells. However, there is no established criterion to verify the minimum qualification to select one from numerous candidates, especially for SHEDs' cultured FBS-free medium for clinic application. For that, we performed a characteristic analysis containing the growth rate, colony-forming unit (CFU) number, average colony size, and migration capacity with hPL-cultured SHEDs from 21 different donors, and we suggest the result as a minimum standard to filter out unqualified candidates. In addition, in the secretome analysis to predict the paracrine effect, it was found that upregulated proteins compared to the control were related to angiogenesis, immune response, and BMP signaling, and this was found to have a strong correlation only with protein concentration. This study presents a minimum standard for selecting cell therapy candidates and suggests the protein concentration of a conditioned medium as a cost-effective tool to expect the paracrine effect of SHEDs.
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Affiliation(s)
- Ji-Young Yoon
- Research Institute for Stem Cell & Matters, Cell & Matter Corporation, Cheonan 31116, Republic of Korea; (J.-Y.Y.); (B.D.Q.)
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.H.L.); (H.-W.K.)
| | - Bình Do Quang
- Research Institute for Stem Cell & Matters, Cell & Matter Corporation, Cheonan 31116, Republic of Korea; (J.-Y.Y.); (B.D.Q.)
| | - Ji-Sun Shin
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.-S.S.); (J.-B.K.)
| | - Jong-Bin Kim
- Department of Pediatric Dentistry, College of Dentistry, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.-S.S.); (J.-B.K.)
| | - Jun Hee Lee
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.H.L.); (H.-W.K.)
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Mechanobiology Dental Medicine Research Center, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Cell & Matter Institute, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Republic of Korea
| | - Hae-Won Kim
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.H.L.); (H.-W.K.)
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Mechanobiology Dental Medicine Research Center, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Cell & Matter Institute, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Republic of Korea
| | - Jung-Hwan Lee
- Research Institute for Stem Cell & Matters, Cell & Matter Corporation, Cheonan 31116, Republic of Korea; (J.-Y.Y.); (B.D.Q.)
- Institute of Tissue Regeneration Engineering (ITREN), Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea; (J.H.L.); (H.-W.K.)
- Department of Nanobiomedical Science & BK21 FOUR NBM Global Research Center for Regenerative Medicine, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Mechanobiology Dental Medicine Research Center, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Cell & Matter Institute, Dankook University, 119 Dandae-ro, Cheonan 31116, Republic of Korea
- Department of Biomaterials Science, School of Dentistry, Dankook University, Cheonan 31116, Republic of Korea
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Shahbazi AS, Irandoost F, Mahdavian R, Shojaeilangari S, Allahvardi A, Naderi-Manesh H. A multi-stage weakly supervised design for spheroid segmentation to explore mesenchymal stem cell differentiation dynamics. BMC Bioinformatics 2025; 26:20. [PMID: 39825265 PMCID: PMC11742216 DOI: 10.1186/s12859-024-06031-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 12/27/2024] [Indexed: 01/20/2025] Open
Abstract
There is a growing interest in utilizing 3D culture models for stem cell and cancer cell research due to their closer resemblance to in vivo environments. In this study, human mesenchymal stem cells (MSCs) were cultured using adipocytes and osteocytes as differentiative mediums on varying concentrations of chitosan substrate. Light microscopy was employed to capture cell images from the first day to the 21st day of differentiation. Accurate image segmentation is crucial for analyzing the morphological features of the spheroids during the experimental period and for understanding MSC differentiation dynamics for therapeutic applications. Therefore, we developed an innovative, weakly supervised model, aided by convolutional neural networks, to perform label-free spheroid segmentation. Since obtaining pixel-level ground truth labels through manual annotation is labor-intensive, our approach improves the overall quality of the ground-truth map by incorporating a multi-stage process within a weakly supervised learning framework. Additionally, we developed a robust learning scheme for spheroid detection, providing a reliable foundation to study MSC differentiation dynamics. The proposed framework was systematically evaluated using low-resolution microscopic data and challenging, noisy backgrounds. The experimental results demonstrate the effectiveness of our segmentation approach in accurately separating the spheroid from the background. Furthermore, it achieves performance comparable to fully supervised state-of-the-art approaches. To quantitatively evaluate our algorithm, extensive experiments were conducted using available annotated data, confirming the reliability and robustness of our method. Our computationally extracted features can confirm the experimental results regarding alterations in MSC viability, attachment, and differentiation dynamics among the substrates with three concentrations of chitosan used. We observed the formation of more compact spheroids with higher solidity and convex area, resulting improved cell attachment and viability on the 2% chitosan substrate. Additionally, this substrate exhibited a higher propensity for differentiation into osteocytes, as evidenced by the formation of smaller and more ellipsoid spheroids. "Chitosan biofilms mimic in vivo environments for stem cell culture, advancing therapeutic and fundamental applications.” "Innovative weakly supervised model enables label-free spheroid segmentation in stem cell differentiation studies.” "Robust learning scheme achieves accurate spheroid separation, comparable to state-of-the-art approaches.”
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Affiliation(s)
- Arash Shahbazpoor Shahbazi
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran
| | - Farzin Irandoost
- Department of Physics, Shahid Beheshti University (SBU Physics), Tehran, Iran
| | - Reza Mahdavian
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran
| | - Seyedehsamaneh Shojaeilangari
- Biomedical Engineering Group, Department of Electrical and Information Technology, Iranian Research Organization for Science and Technology (IROST), Tehran, 33535111, Iran.
| | - Abdollah Allahvardi
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran
| | - Hossein Naderi-Manesh
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115-111, Iran.
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Sousa AC, Alvites R, Lopes B, Sousa P, Moreira A, Coelho A, Santos JD, Atayde L, Alves N, Maurício AC. Three-Dimensional Printing/Bioprinting and Cellular Therapies for Regenerative Medicine: Current Advances. J Funct Biomater 2025; 16:28. [PMID: 39852584 PMCID: PMC11765675 DOI: 10.3390/jfb16010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Revised: 01/10/2025] [Accepted: 01/11/2025] [Indexed: 01/26/2025] Open
Abstract
The application of three-dimensional (3D) printing/bioprinting technologies and cell therapies has garnered significant attention due to their potential in the field of regenerative medicine. This paper aims to provide a comprehensive overview of 3D printing/bioprinting technology and cell therapies, highlighting their results in diverse medical applications, while also discussing the capabilities and limitations of their combined use. The synergistic combination of 3D printing and cellular therapies has been recognised as a promising and innovative approach, and it is expected that these technologies will progressively assume a crucial role in the treatment of various diseases and conditions in the foreseeable future. This review concludes with a forward-looking perspective on the future impact of these technologies, highlighting their potential to revolutionize regenerative medicine through enhanced tissue repair and organ replacement strategies.
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Affiliation(s)
- Ana Catarina Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Rui Alvites
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
- Instituto Universitário de Ciências da Saúde (CESPU), Instituto Universitário de Ciências da Saúde (IUCS), Avenida Central de Gandra 1317, Gandra, 4585-116 Paredes, Portugal
| | - Bruna Lopes
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Patrícia Sousa
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Alícia Moreira
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - André Coelho
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - José Domingos Santos
- REQUIMTE-LAQV, Departamento de Engenharia Metalúrgica e Materiais, Faculdade de Engenharia, UP, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal;
| | - Luís Atayde
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
| | - Nuno Alves
- Centre for Rapid and Sustainable Product Development (CDRSP), Polytechnic Institute of Leiria, Rua de Portugal—Zona Industrial, 2430-028 Marinha Grande, Portugal;
| | - Ana Colette Maurício
- Departamento de Clínicas Veterinárias, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Universidade do Porto (UP), Rua de Jorge Viterbo Ferreira, nº 228, 4050-313 Porto, Portugal; (A.C.S.); (R.A.); (B.L.); (P.S.); (A.M.); (A.C.); (L.A.)
- Centro de Estudos de Ciência Animal (CECA), Instituto de Ciências, Tecnologias e Agroambiente da Universidade do Porto (ICETA), Rua D. Manuel II, Apartado 55142, 4051-401 Porto, Portugal
- Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), Av. Universidade Técnica, 1300-477 Lisboa, Portugal
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8
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Raju PS, Sriraghavan MR, Jayaraman P, Balasubramaniam B, Karuppiah KS, Kumararaja P. Efficacy of Ultrasound-Guided Injection of Platelet-Rich Plasma in Treatment of Sports-Related Meniscal Injuries. Indian J Radiol Imaging 2025; 35:10-16. [PMID: 39697506 PMCID: PMC11651871 DOI: 10.1055/s-0044-1788554] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2024] Open
Abstract
Purpose Meniscal injuries are a common occurrence in sports-related activities, often leading to pain, reduced joint function, and impaired athletic performance. This study aimed to evaluate the role of ultrasound-guided intra-articular platelet-rich plasma (PRP)-rich fluid injection which was obtained through serial centrifugation in the treatment of meniscal injuries resulting from sports activities. Materials and Methods A prospective study was conducted involving 54 cases with grade I, II, and III meniscal injuries, aged 18 and 43 years. PRP-rich fluid was prepared by subjecting autologous blood samples to a two-step centrifugation process. Patients were assessed pretreatment and at regular intervals posttreatment. Results Patients reported reduced pain and improved joint functionality following treatment. Average age of the patients was 34.4 years, and average follow-up period was 275.1 days. It is noteworthy that no cases of bilateral meniscal injuries were identified; indicating that the focus was primarily on single knee injuries. Predominance of grade II injuries suggests that the PRP intervention might be particularly effective in addressing more severe meniscal tears. Conclusion The results of our study provide compelling evidence for the positive impact of PRP augmentation in meniscus repair. Our findings indicate that PRP therapy has the potential to bring about substantial benefits for individuals with meniscus tears of the knee, particularly in terms of pain relief and enhanced functional capabilities.
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Affiliation(s)
- Prabakar Singh Raju
- Department of Arthroscopy and Sports Medicine, Tamil Nadu Government Multi-Super-Specialty Hospital, Chennai, Tamil Nadu, India
| | - Makesh Ram Sriraghavan
- Department of Arthroscopy and Sports Medicine, Tamil Nadu Government Multi-Super-Specialty Hospital, Chennai, Tamil Nadu, India
| | - Pazhani Jayaraman
- Department of Arthroscopy and Sports Medicine, Tamil Nadu Government Multi-Super-Specialty Hospital, Chennai, Tamil Nadu, India
| | - Bheeshma Balasubramaniam
- Department of Arthroscopy and Sports Medicine, Tamil Nadu Government Multi-Super-Specialty Hospital, Chennai, Tamil Nadu, India
| | - Karthik Shanmugavel Karuppiah
- Department of Arthroscopy and Sports Medicine, Tamil Nadu Government Multi-Super-Specialty Hospital, Chennai, Tamil Nadu, India
| | - Poornima Kumararaja
- Department of Pathology, ACS Medical College and Hospital, Chennai, Tamil Nadu, India
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9
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Banerjee K, Mandal S, Nath A, Chakraborty SB, Mitra A, Gupta S. Thyroxine (T3)-mediated regulation of early cardiac repair in a chemical-induced hypoxia/reoxygenation model of adult zebrafish (Danio rerio). Wound Repair Regen 2025; 33:e13244. [PMID: 39727215 DOI: 10.1111/wrr.13244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 11/24/2024] [Accepted: 12/09/2024] [Indexed: 12/28/2024]
Abstract
Hypoxia-mediated cardiac tissue injury and its repair or regeneration are one of the major health management challenges globally. Unlike mammals, lower vertebrate species such as zebrafish (Danio rerio) represent a natural model to study cardiac injury, repair and regeneration. Thyroxine (T3) has been hypothesised to be one of the endocrine factors responsible for the evolutionary trade-off for acquiring endothermy and regenerative capability in higher vertebrates. However, the specific targets of T3 during cardiac repair are still obscure. In this study, cardiac injury was generated in adult zebrafish by acute anaemia-induced hypoxia/reoxygenation (H/R) in the presence or absence of exogenous T3 alone or along with 1-850 (inhibitor of T3 receptor) and iopanoic acid (IOA, blocker of T3 release), respectively. A microarray analysis showed that 10,226 gene expression changes in expression across all experimental groups, providing a comprehensive understanding of the cardiac transcriptome. Analysis of 11 candidate genes was conducted using qRT-PCR and the findings aligned with the microarray data. Histological assessment by Masson's trichrome staining and immunofluorescence studies also corroborated the microarray data. GO enrichment analysis showed noteworthy involvement of T3 in the modulation of genes involved in oxidative stress, cardiac fibrosis, energy metabolism, autophagy, apoptosis and regeneration during the initial repair phase (7 days) of H/R-damaged cardiac tissue. Overall, this is the first study that presents a holistic picture of cardiac repair and regeneration post H/R injury in zebrafish and the effect of T3 pre-treatment on it.
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Affiliation(s)
- Kalyan Banerjee
- Department of Zoology, Trivenidevi Bhalotia College, Raniganj, West Bengal, India
| | - Subhadeep Mandal
- Department of Zoology, Trivenidevi Bhalotia College, Raniganj, West Bengal, India
| | - Arghya Nath
- Department of Zoology, University of Burdwan, Bardhaman, West Bengal, India
| | | | - Arkadeep Mitra
- Department of Zoology, City College, Kolkata, West Bengal, India
| | - Shreyasi Gupta
- Department of Zoology, Trivenidevi Bhalotia College, Raniganj, West Bengal, India
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10
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Sunami H, Shimizu Y, Nakasone H, Futenma N, Denda J, Yokota S, Kishimoto H, Makita M, Nishikawa Y. In vivo imaging of adipose-derived stem cell sheets on biodegradable nonwoven fabric using X-ray CT. Biomed Eng Online 2024; 23:133. [PMID: 39731095 DOI: 10.1186/s12938-024-01324-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 12/11/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND A biodegradable nonwoven fabric that can be used to extract adipose-derived stem cells (ADSCs) from adipose tissue slices was developed, which were cultured rapidly without enzymatic treatment. The extracted and cultured ADSCs remain on the nonwoven fabric and form a thick cell sheet. The aim was to use the thick cell sheet as a treatment by transplanting it into the living body. In addition, the expectation was that it will be possible to observe the cell sheet in the living body using X-ray computed tomography (CT) because the nonwoven fabric used to produce the cell sheet contains 50% (by weight) hydroxyapatite. RESULTS Thick cell sheets of ADSCs supported by two layers of nonwoven fabric were cut to size and transplanted into the cheeks of rats. No health damage was observed in the rats in which the cell sheets were implanted, except for one in which the surgery appeared to have failed. X-ray CT imaging showed that the fabric of the implanted cell sheet biodegraded over 12 weeks. Changes in the position, shape, and size of the cell sheet within the rat's body were tracked by X-ray CT. The thick cell sheets, which can be easily produced by simply seeding tissue slices, can be cut into appropriate shapes and transplanted safely, and it was confirmed that they slowly biodegraded when transplanted into the rats' bodies. CONCLUSIONS We demonstrated not only that the thick ADSC sheets can be transplanted successfully into animals, but also that the transplanted sheets can be observed in vivo by X-ray CT, which also allows changes in the ADSC sheets to be tracked. The results suggest that the biodegradable nonwoven fabric will be a useful transplantation device to ensure cell engraftment throughout the affected area, and facilitate monitoring of the transplant's subsequent status. We expect that this transplantation device will promote the development of regenerative therapy.
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Affiliation(s)
- Hiroshi Sunami
- Faculty of Medicine, University of the Ryukyus, Nishihara-cho, Japan.
| | - Yusuke Shimizu
- Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Japan
- University of the Ryukyus Hospital, Nishihara-cho, Japan
| | | | - Naoko Futenma
- University of the Ryukyus Hospital, Nishihara-cho, Japan
| | - Junko Denda
- Faculty of Medicine, University of the Ryukyus, Nishihara-cho, Japan
| | - Sayaka Yokota
- University of the Ryukyus Hospital, Nishihara-cho, Japan
| | - Hidehiro Kishimoto
- Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Japan
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11
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Horie T, Hirata H, Sakamoto T, Kitajima H, Fuku A, Nakamura Y, Sunatani Y, Tanida I, Sunami H, Tachi Y, Ishigaki Y, Yamamoto N, Shimizu Y, Ichiseki T, Kaneuji A, Iwabuchi K, Osawa S, Kawahara N. Multiomics analyses reveal adipose-derived stem cells inhibit the inflammatory response of M1-like macrophages through secreting lactate. Stem Cell Res Ther 2024; 15:485. [PMID: 39696485 DOI: 10.1186/s13287-024-04072-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Accepted: 11/20/2024] [Indexed: 12/20/2024] Open
Abstract
BACKGROUND Adipose-derived stem cells (ADSCs) are widely used in the field of regenerative medicine because of their various functions, including anti-inflammatory effects. ADSCs are considered to exert their anti-inflammatory effects by secreting anti-inflammatory cytokines and extracellular vesicles. Although recent studies have reported that metabolites have a variety of physiological activities, whether those secreted by ADSCs have anti-inflammatory properties remains unclear. Here, we performed multiomics analyses to examine the effect of ADSC-derived metabolites on M1-like macrophages, which play an important role in inflammatory responses. METHODS The concentration of metabolites in the culture supernatant of ADSCs was quantified using capillary electrophoresis time-of-flight mass spectrometry. To evaluate their effects on inflammatory responses, M1-like macrophages were exposed to the conditioned ADSC medium or their metabolites, and RNA sequencing was used to detect gene expression changes. Immunoblotting was performed to examine how the metabolite suppresses inflammatory processes. To clarify the contribution of the metabolite in the conditioned medium to its anti-inflammatory effects, metabolite uptake was pharmacologically inhibited, and gene expression and the tumor necrosis factor-α concentration were measured by quantitative PCR and enzyme-linked immunosorbent assay, respectively. RESULTS Metabolomic analysis showed large amounts of lactate in the culture supernatant. The conditioned medium and lactate significantly suppressed or increased the pro-inflammatory and anti-inflammatory gene expressions. However, sequencing and immunoblotting analysis revealed that lactate did not induce polarization from M1- to M2-like macrophages. Based on a recent report that the immunosuppressive effect of lactate depends on epigenetic reprogramming, histone acetylation was investigated, and H3K27ac expression was upregulated. In addition, 7ACC2, which specifically inhibits the monocarboxylate transporter 1, significantly inhibited the anti-inflammatory effect of the conditioned ADSC medium on M1-like macrophages. CONCLUSIONS Our results showed that ADSCs suppress pro-inflammatory effects of M1-like macrophages by secreting lactate. This study adds to our understanding of the importance of metabolites and is also expected to elucidate new mechanisms of ADSC treatments.
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Affiliation(s)
- Tetsuhiro Horie
- Medical Research Institute, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
- Department of Pharmacy, Kanazawa Medical University Hospital, Kahoku, Ishikawa, 920-0293, Japan
| | - Hiroaki Hirata
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan.
| | - Takuya Sakamoto
- Medical Research Institute, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
- Department of Pharmacy, Kanazawa Medical University Hospital, Kahoku, Ishikawa, 920-0293, Japan
| | - Hironori Kitajima
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Atsushi Fuku
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Yuka Nakamura
- Medical Research Institute, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Yumi Sunatani
- Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Ikuhiro Tanida
- Genome Biotechnology Laboratory, Kanazawa Institute of Technology, Hakusan, Ishikawa, 924-0838, Japan
| | - Hiroshi Sunami
- Advanced Medical Research Center, Faculty of Medicine, University of the Ryukyus, Nakagami, Okinawa, 903-0215, Japan
| | - Yoshiyuki Tachi
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Yasuhito Ishigaki
- Medical Research Institute, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Naoki Yamamoto
- Research Promotion Headquarters, Fujita Health University, Toyoake, Aichi, 470-1192, Japan
| | - Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Nakagami, Okinawa, 903-0215, Japan
| | - Toru Ichiseki
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan.
| | - Ayumi Kaneuji
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Kuniyoshi Iwabuchi
- Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
| | - Satoshi Osawa
- Genome Biotechnology Laboratory, Kanazawa Institute of Technology, Hakusan, Ishikawa, 924-0838, Japan
| | - Norio Kawahara
- Department of Orthopedic Surgery, Kanazawa Medical University, Kahoku, Ishikawa, 920-0293, Japan
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12
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Oeller M, Schally T, Zimmermann G, Lauth W, Schallmoser K, Rohde E, Laner-Plamberger S. Heparin Differentially Regulates the Expression of Specific miRNAs in Mesenchymal Stromal Cells. Int J Mol Sci 2024; 25:12589. [PMID: 39684301 DOI: 10.3390/ijms252312589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 11/13/2024] [Accepted: 11/21/2024] [Indexed: 12/18/2024] Open
Abstract
In regenerative medicine, stromal cells are supposed to play an important role by modulating immune responses and differentiating into various tissue types. The aim of this study was to investigate the influence of heparin, frequently used as an anticoagulant in human platelet lysate (HPL)-supplemented cell cultures, on the expression of non-coding RNA species, particularly microRNAs (miRNA), which are pivotal regulators of gene expression. Through genomic analysis and quantitative RT-PCR, we assessed the differential impact of heparin on miRNA expression in various stromal cell types, derived from human bone marrow, umbilical cord and white adipose tissue. Our results demonstrate that heparin significantly alters miRNA expression, with distinct up- and downregulation patterns depending on the original tissue source of human stromal cells. Furthermore, our analyses indicate that these heparin-induced alterations in miRNA expression profiles influence critical cellular processes, including proliferation, apoptosis and differentiation. In conclusion, our study highlights that heparin not only fulfills its primary role as an efficient anticoagulant but can also modulate important regulatory pathways in stromal cells by influencing miRNA expression. This may alter cellular properties and thus influence stromal cell-based therapeutic applications in regenerative medicine.
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Affiliation(s)
- Michaela Oeller
- Department for Transfusion Medicine, University Hospital of Salzburg (SALK), Paracelsus Medical University (PMU) Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
| | - Tanja Schally
- GMP Laboratory, PMU Salzburg, Strubergasse 21, 5020 Salzburg, Austria
| | - Georg Zimmermann
- Team Biostatistics and Big Medical Data, IDA Lab Salzburg, PMU Salzburg, Strubergasse 16, 5020 Salzburg, Austria
- Research Program Biomedical Data Science, PMU Salzburg, Strubergasse 16, 5020 Salzburg, Austria
- Department of Artificial Intelligence and Human Interfaces, Faculty of Digital and Analytical Sciences, Paris Lodron University Salzburg, Jakob Haringer Straße 2, 5020 Salzburg, Austria
| | - Wanda Lauth
- Team Biostatistics and Big Medical Data, IDA Lab Salzburg, PMU Salzburg, Strubergasse 16, 5020 Salzburg, Austria
- Research Program Biomedical Data Science, PMU Salzburg, Strubergasse 16, 5020 Salzburg, Austria
| | - Katharina Schallmoser
- Department for Transfusion Medicine, University Hospital of Salzburg (SALK), Paracelsus Medical University (PMU) Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
| | - Eva Rohde
- Department for Transfusion Medicine, University Hospital of Salzburg (SALK), Paracelsus Medical University (PMU) Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
- GMP Laboratory, PMU Salzburg, Strubergasse 21, 5020 Salzburg, Austria
| | - Sandra Laner-Plamberger
- Department for Transfusion Medicine, University Hospital of Salzburg (SALK), Paracelsus Medical University (PMU) Salzburg, Muellner Hauptstraße 48, 5020 Salzburg, Austria
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13
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Trubin S, Patel DB, Tian A. Regulation of the Intestinal Stem Cell Pool and Proliferation in Drosophila. Cells 2024; 13:1856. [PMID: 39594605 PMCID: PMC11592481 DOI: 10.3390/cells13221856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/07/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024] Open
Abstract
Understanding the regulation of somatic stem cells, both during homeostasis and in response to environmental challenges like injury, infection, chemical exposure, and nutritional changes, is critical because their dysregulation can result in tissue degeneration or tumorigenesis. The use of models such as the Drosophila and mammalian adult intestines offers valuable insights into tissue homeostasis and regeneration, advancing our knowledge of stem cell biology and cancer development. This review highlights significant findings from recent studies, unveiling the molecular mechanisms that govern self-renewal, proliferation, differentiation, and regeneration of intestinal stem cells (ISCs). These insights not only enhance our understanding of normal tissue maintenance but also provide critical perspectives on how ISC dysfunction can lead to pathological conditions such as colorectal cancer (CRC).
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Affiliation(s)
- Simona Trubin
- Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, Louisiana Cancer Research Center, New Orleans, LA 70112, USA
| | - Dhruv B. Patel
- Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, Louisiana Cancer Research Center, New Orleans, LA 70112, USA
| | - Aiguo Tian
- Department of Biochemistry and Molecular Biology, Tulane University School of Medicine, Louisiana Cancer Research Center, New Orleans, LA 70112, USA
- Tulane Aging Center, Tulane University School of Medicine, New Orleans, LA 70112, USA
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14
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Zhang Y, Xia Y, Zhang R, Zhou X, Jiang J. Urine-Derived Stem Cells Reverse Bleomycin‑Induced Experimental Pulmonary Fibrosis by Inhibition of the TGF-β1-Smad2/3 Pathway. Cytotherapy 2024; 26:1236-1244. [PMID: 38852093 DOI: 10.1016/j.jcyt.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Revised: 05/07/2024] [Accepted: 05/14/2024] [Indexed: 06/10/2024]
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is characterized by progressive lung interstitial lesions with the disease pathophysiology incompletely understood, which is a serious and fatal disorder with limited treatment options. Mesenchymal stem cells (MSCs) have exhibited promising therapeutic capability for IPF. While most types of MSCs are obtained invasively, urine-derived stem cells (USCs) can be gained in a safe, noninvasive, and inexpensive procedure, which are readily available and reported to exhibit no risk of teratoma formation or oncogenic potential in vivo, sounding alternative to other MSCs. This study aims to investigate the therapeutic effect and mechanism of USCs on IPF, using a bleomycin (BLM)-induced IPF model in mice. METHODS Cell surface marker examination by flow cytometry analysis and cell differentiation culture were used to characterize USCs obtained from healthy individuals. BLM was instilled endotracheally in adult C57BL/6 mice, followed by USCs or human bone marrow-derived mesenchymal stem cells (BMSCs) treatment by tail vein injection on day 14. Mice were euthanized on day 14 before administration or day 21 for the evaluation of pulmonary histopathology and hydroxyproline (HYP) content. Inflammatory factors of the lung, including transforming growth factor (TGF)-β1, TNF-α, IL-6, MMP2 were analyzed by quantitative real-time PCR (qRT-PCR). Additionally, immunohistochemistry (IHC) and western blotting (WB) were applied to evaluate the expression of α-SMA and activation of TGF-β1-Smad2/3 in lung. RESULTS USCs highly expressed CD29 and CD90, showing negative expression of hematopoietic stem cell markers (CD45, CD34) and could differentiate into, at least, bone and fat in vitro. In mice challenged with BLM, septal thickening and prominent fibrosis were observed on day 14, with higher HYP content and mRNA levels of TGF-β1, TNF-α and IL-6 exhibited, compared to untreated mice. USCs could migrate to lung and accumulate there in mouse model after intravenous injection. Transplantation of USCs into BLM-induced mice improved their pulmonary histopathology, decreasing Ashcroft score, Szapiel score, HYP content and mRNA levels of TGF-β1 and MMP2 of lung, similar to the effects of BMSCs. IHC and WB further revealed that USCs could inhibit activation of the TGF‑β1-Smad2/3 pathway of lung in vivo. CONCLUSIONS Transplantation of USCs effectively reverses pulmonary fibrotic phenotype in an experimental IPF model, inhibiting the TGF-β1-Smad2/3 pathway, a key driver of fibrosis. These results suggest the therapeutic application of USCs for IPF, instead of other types of MSCs obtained invasively.
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Affiliation(s)
- Yanju Zhang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; Infection Management Office, Affiliated Hospital of Nantong University, Nantong, China; Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China
| | - Yunfei Xia
- Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong, China
| | - Rui Zhang
- Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Xiaodi Zhou
- Infection Management Office, Affiliated Hospital of Nantong University, Nantong, China
| | - Junhong Jiang
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Pulmonary and Critical Care Medicine, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, China.
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15
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Montenegro F, Giannuzzi F, Picerno A, Cicirelli A, Stea ED, Di Leo V, Sallustio F. How Stem and Progenitor Cells Can Affect Renal Diseases. Cells 2024; 13:1460. [PMID: 39273032 PMCID: PMC11393889 DOI: 10.3390/cells13171460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 08/26/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024] Open
Abstract
Stem and progenitor cells have been observed to contribute to regenerative processes in acute renal failure and chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem and progenitor cells exert their influence on kidney diseases. Understanding how these cells integrate with the existing renal architecture and their response to injury could pave the way for innovative treatment strategies aimed at promoting kidney repair and regeneration. Overall, the role of stem and progenitor cells in kidney diseases is multifaceted, with their ability to contribute to tissue regeneration, immune modulation, and the maintenance of renal homeostasis. Here, we review the studies that we have available today about the involvement of stem and progenitor cells both in regenerative therapies and in the causes of renal diseases, as well as in natural healing mechanisms, taking into account the main kidney disorders, such as IgA nephropathy, lupus nephritis, diabetic nephropathy, C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous nephropathy, anti-glomerular basement membrane glomerulonephritis, and ANCA-associated crescentic glomerulonephritis. Moreover, based on the comprehensive data available in the framework of the specific kidney diseases on stem cells and renal progenitors, we hypothesize a possible role of adult renal progenitors in exacerbating or recovering the illness.
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Affiliation(s)
- Francesca Montenegro
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy; (F.M.); (F.G.); (A.P.); (A.C.); (V.D.L.)
| | - Francesca Giannuzzi
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy; (F.M.); (F.G.); (A.P.); (A.C.); (V.D.L.)
| | - Angela Picerno
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy; (F.M.); (F.G.); (A.P.); (A.C.); (V.D.L.)
| | - Antonella Cicirelli
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy; (F.M.); (F.G.); (A.P.); (A.C.); (V.D.L.)
| | - Emma Diletta Stea
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, 70124 Bari, Italy;
| | - Vincenzo Di Leo
- Department of Interdisciplinary Medicine, University of Bari Aldo Moro, 70124 Bari, Italy; (F.M.); (F.G.); (A.P.); (A.C.); (V.D.L.)
| | - Fabio Sallustio
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari Aldo Moro, 70124 Bari, Italy;
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16
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Jeyaraman N, Shrivastava S, Ravi VR, Nallakumarasamy A, Pundkar A, Jeyaraman M. Understanding and controlling the variables for stromal vascular fraction therapy. World J Stem Cells 2024; 16:784-798. [PMID: 39219728 PMCID: PMC11362852 DOI: 10.4252/wjsc.v16.i8.784] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 06/13/2024] [Accepted: 07/25/2024] [Indexed: 08/26/2024] Open
Abstract
In regenerative medicine, the isolation of mesenchymal stromal cells (MSCs) from the adipose tissue's stromal vascular fraction (SVF) is a critical area of study. Our review meticulously examines the isolation process of MSCs, starting with the extraction of adipose tissue. The choice of liposuction technique, anatomical site, and immediate processing are essential to maintain cell functionality. We delve into the intricacies of enzymatic digestion, emphasizing the fine-tuning of enzyme concentrations to maximize cell yield while preventing harm. The review then outlines the filtration and centrifugation techniques necessary for isolating a purified SVF, alongside cell viability assessments like flow cytometry, which are vital for confirming the efficacy of the isolated MSCs. We discuss the advantages and drawbacks of using autologous vs allogeneic SVF sources, touching upon immunocompatibility and logistical considerations, as well as the variability inherent in donor-derived cells. Anesthesia choices, the selection between hypodermic needles vs liposuction cannulas, and the role of adipose tissue lysers in achieving cellular dissociation are evaluated for their impact on SVF isolation. Centrifugation protocols are also analyzed for their part in ensuring the integrity of the SVF. The necessity for standardized MSC isolation protocols is highlighted, promoting reproducibility and successful clinical application. We encourage ongoing research to deepen the understanding of MSC biology and therapeutic action, aiming to further the field of regenerative medicine. The review concludes with a call for rigorous research, interdisciplinary collaboration, and strict adherence to ethical and regulatory standards to safeguard patient safety and optimize treatment outcomes with MSCs.
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Affiliation(s)
- Naveen Jeyaraman
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Sandeep Shrivastava
- Department of Orthopaedics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
| | - V R Ravi
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Arulkumar Nallakumarasamy
- Department of Orthopaedics, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
| | - Aditya Pundkar
- Department of Orthopaedics, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha 442004, Maharashtra, India
| | - Madhan Jeyaraman
- Department of Regenerative Medicine, Mother Cell Regenerative Centre, Tiruchirappalli 620017, Tamil Nadu, India
- Department of Orthopaedics, ACS Medical College and Hospital, Dr MGR Educational and Research Institute, Chennai 600077, Tamil Nadu, India.
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Goraltchouk A, Lourie J, Hollander JM, Grace Rosen H, Fujishiro AA, Luppino F, Zou K, Seregin A. Development and characterization of a first-in-class adjustable-dose gene therapy system. Gene 2024; 919:148500. [PMID: 38663689 DOI: 10.1016/j.gene.2024.148500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 04/11/2024] [Accepted: 04/22/2024] [Indexed: 05/06/2024]
Abstract
INTRODUCTION Despite significant potential, gene therapy has been relegated to the treatment of rare diseases, due in part to an inability to adjust dosage following initial administration. Other significant constraints include cost, specificity, antigenicity, and systemic toxicity of current generation technologies. To overcome these challenges, we developed a first-in-class adjustable-dose gene therapy system, with optimized biocompatibility, localization, durability, and cost. METHODS A lipid nanoparticle (LNP) delivery system was developed and characterized by dynamic light scattering for size, zeta potential, and polydispersity. Cytocompatibility and transfection efficiency were optimized in vitro using primary human adipocytes and preadipocytes. Durability, immunogenicity, and adjustment of expression were evaluated in C57BL/6 and B6 albino mice using in vivo bioluminescence imaging. Biodistribution was assessed by qPCR and immunohistochemistry; therapeutic protein expression was quantified by ELISA. RESULTS Following LNP optimization, in vitro transfection efficiency of primary human adipocytes reached 81.3 % ± 8.3 % without compromising cytocompatibility. Critical physico-chemical properties of the system (size, zeta potential, polydispersity) remained stable over a broad range of genetic cassette sizes (1,871-6,203 bp). Durable expression was observed in vivo over 6 months, localizing to subcutaneous adipose tissues at the injection site with no detectable transgene in the liver, heart, spleen, or kidney. Gene expression was adjustable using several physical and pharmacological approaches, including cryolipolysis, focused ultrasound, and pharmacologically inducible apoptosis. The ability of transfected adipocytes to express therapeutic transgenes ranging from peptides to antibodies, at potentially clinically relevant levels, was confirmed in vitro and in vivo. CONCLUSION We report the development of a novel, low-cost therapeutic platform, designed to enable the replacement of subcutaneously administered protein treatments with a single-injection, adjustable-dose gene therapy.
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Affiliation(s)
- Alex Goraltchouk
- Remedium Bio, Inc. 1116 Great Plain Ave, Suite 203, Needham, MA 02492, United States of America
| | - Jared Lourie
- Department of Exercise and Health Sciences, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, United States of America
| | - Judith M Hollander
- Remedium Bio, Inc. 1116 Great Plain Ave, Suite 203, Needham, MA 02492, United States of America
| | - H Grace Rosen
- Department of Biology, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, United States of America
| | - Atsutaro A Fujishiro
- Department of Exercise and Health Sciences, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, United States of America
| | - Francesco Luppino
- Remedium Bio, Inc. 1116 Great Plain Ave, Suite 203, Needham, MA 02492, United States of America
| | - Kai Zou
- Department of Exercise and Health Sciences, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, United States of America
| | - Alexey Seregin
- Remedium Bio, Inc. 1116 Great Plain Ave, Suite 203, Needham, MA 02492, United States of America.
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Re F, Sartore L, Pasini C, Ferroni M, Borsani E, Pandini S, Bianchetti A, Almici C, Giugno L, Bresciani R, Mutti S, Trenta F, Bernardi S, Farina M, Russo D. In Vitro Biocompatibility Assessment of Bioengineered PLA-Hydrogel Core-Shell Scaffolds with Mesenchymal Stromal Cells for Bone Regeneration. J Funct Biomater 2024; 15:217. [PMID: 39194655 DOI: 10.3390/jfb15080217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/22/2024] [Accepted: 07/25/2024] [Indexed: 08/29/2024] Open
Abstract
Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core-shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin-chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration.
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Affiliation(s)
- Federica Re
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
- Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, 25123 Brescia, Italy
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
| | - Luciana Sartore
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Materials Science and Technology Laboratory, Department of Mechanical and Industrial Engineering, University of Brescia, 25123 Brescia, Italy
| | - Chiara Pasini
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Materials Science and Technology Laboratory, Department of Mechanical and Industrial Engineering, University of Brescia, 25123 Brescia, Italy
| | - Matteo Ferroni
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Department of Civil, Environmental, Architectural Engineering and Mathematics (DICATAM), University of Brescia, Via Valotti 9, 25123 Brescia, Italy
- National Research Council (CNR)-Institute for Microelectronics and Microsystems, Via Gobetti 101, 40129 Bologna, Italy
| | - Elisa Borsani
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
- Interdepartmental University Center of Research "Adaption and Regeneration of Tissues and Organs (ARTO)", University of Brescia, 25123 Brescia, Italy
| | - Stefano Pandini
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Materials Science and Technology Laboratory, Department of Mechanical and Industrial Engineering, University of Brescia, 25123 Brescia, Italy
| | - Andrea Bianchetti
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Laboratory for Stem Cells Manipulation and Cryopreservation, Department of Transfusion Medicine, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
| | - Camillo Almici
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- Laboratory for Stem Cells Manipulation and Cryopreservation, Department of Transfusion Medicine, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
| | - Lorena Giugno
- Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, 25123 Brescia, Italy
| | - Roberto Bresciani
- Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
- Highly Specialized Laboratory, ASST Spedali Civili di Brescia, 25123 Brescia, Italy
| | - Silvia Mutti
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
- Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, 25123 Brescia, Italy
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
| | - Federica Trenta
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
- Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, 25123 Brescia, Italy
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
| | - Simona Bernardi
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
- Centro di Ricerca Emato-Oncologica AIL (CREA), ASST Spedali Civili, 25123 Brescia, Italy
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
- National Center for Gene Therapy and Drugs based on RNA Technology-CN3, 35122 Padua, Italy
| | - Mirko Farina
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
| | - Domenico Russo
- Unit of Blood Diseases and Cell Therapies, Department of Clinical and Experimental Sciences, University of Brescia, "ASST-Spedali Civili" Hospital of Brescia, 25123 Brescia, Italy
- University Center of Research "STem cells, bioENgineering and regenerative MEDicine"-STENMED, University of Brescia, 25123 Brescia, Italy
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Boraldi F, Lofaro FD, Bonacorsi S, Mazzilli A, Garcia-Fernandez M, Quaglino D. The Role of Fibroblasts in Skin Homeostasis and Repair. Biomedicines 2024; 12:1586. [PMID: 39062158 PMCID: PMC11274439 DOI: 10.3390/biomedicines12071586] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2024] [Revised: 07/08/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Fibroblasts are typical mesenchymal cells widely distributed throughout the human body where they (1) synthesise and maintain the extracellular matrix, ensuring the structural role of soft connective tissues; (2) secrete cytokines and growth factors; (3) communicate with each other and with other cell types, acting as signalling source for stem cell niches; and (4) are involved in tissue remodelling, wound healing, fibrosis, and cancer. This review focuses on the developmental heterogeneity of dermal fibroblasts, on their ability to sense changes in biomechanical properties of the surrounding extracellular matrix, and on their role in aging, in skin repair, in pathologic conditions and in tumour development. Moreover, we describe the use of fibroblasts in different models (e.g., in vivo animal models and in vitro systems from 2D to 6D cultures) for tissue bioengineering and the informative potential of high-throughput assays for the study of fibroblasts under different disease contexts for personalized healthcare and regenerative medicine applications.
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Affiliation(s)
- Federica Boraldi
- Department of Life Science, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (S.B.); (A.M.)
| | - Francesco Demetrio Lofaro
- Department of Life Science, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (S.B.); (A.M.)
| | - Susanna Bonacorsi
- Department of Life Science, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (S.B.); (A.M.)
| | - Alessia Mazzilli
- Department of Life Science, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (S.B.); (A.M.)
| | - Maria Garcia-Fernandez
- Department of Human Physiology, Institute of Biomedical Investigation (IBIMA), University of Málaga, 29010 Málaga, Spain;
| | - Daniela Quaglino
- Department of Life Science, University of Modena and Reggio Emilia, 41125 Modena, Italy; (F.D.L.); (S.B.); (A.M.)
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20
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Shimizu Y, Ntege EH, Inoue Y, Matsuura N, Sunami H, Sowa Y. Optimizing mesenchymal stem cell extracellular vesicles for chronic wound healing: Bioengineering, standardization, and safety. Regen Ther 2024; 26:260-274. [PMID: 38978963 PMCID: PMC11228664 DOI: 10.1016/j.reth.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 05/12/2024] [Accepted: 06/06/2024] [Indexed: 07/10/2024] Open
Abstract
Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.
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Affiliation(s)
- Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Edward Hosea Ntege
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Yoshikazu Inoue
- Department of Plastic and Reconstructive Surgery, School of Medicine, Fujita Health University, 1-98, Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
| | - Naoki Matsuura
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Hiroshi Sunami
- Center for Advanced Medical Research, School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Yoshihiro Sowa
- Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Tochigi, Japan
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21
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Marquez-Curtis LA, Elliott JAW. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects: Update from 2015 review. Cryobiology 2024; 115:104856. [PMID: 38340887 DOI: 10.1016/j.cryobiol.2024.104856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 01/26/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024]
Abstract
Mesenchymal stromal cells (MSCs) have become one of the most investigated and applied cells for cellular therapy and regenerative medicine. In this update of our review published in 2015, we show that studies continue to abound regarding the characterization of MSCs to distinguish them from other similar cell types, the discovery of new tissue sources of MSCs, and the confirmation of their properties and functions that render them suitable as a therapeutic. Because cryopreservation is widely recognized as the only technology that would enable the on-demand availability of MSCs, here we show that although the traditional method of cryopreserving cells by slow cooling in the presence of 10% dimethyl sulfoxide (Me2SO) continues to be used by many, several novel MSC cryopreservation approaches have emerged. As in our previous review, we conclude from these recent reports that viable and functional MSCs from diverse tissues can be recovered after cryopreservation using a variety of cryoprotectants, freezing protocols, storage temperatures, and periods of storage. We also show that for logistical reasons there are now more studies devoted to the cryopreservation of tissues from which MSCs are derived. A new topic included in this review covers the application in COVID-19 of MSCs arising from their immunomodulatory and antiviral properties. Due to the inherent heterogeneity in MSC populations from different sources there is still no standardized procedure for their isolation, identification, functional characterization, cryopreservation, and route of administration, and not likely to be a "one-size-fits-all" approach in their applications in cell-based therapy and regenerative medicine.
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Affiliation(s)
- Leah A Marquez-Curtis
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada, T6G 1H9; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, T6G 1C9
| | - Janet A W Elliott
- Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada, T6G 1H9; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada, T6G 1C9.
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22
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Shirakawa J, Ntege EH, Takemura M, Miyamoto S, Kawano T, Sampei C, Kawabata H, Nakamura H, Sunami H, Hayata T, Shimizu Y. Exploring SSEA3 as an emerging biomarker for assessing the regenerative potential of dental pulp-derived stem cells. Regen Ther 2024; 26:71-79. [PMID: 38828011 PMCID: PMC11139766 DOI: 10.1016/j.reth.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Revised: 04/30/2024] [Accepted: 05/09/2024] [Indexed: 06/05/2024] Open
Abstract
Background Human dental pulp-derived stem cells (hDPSCs) have emerged as a promising source for adult stem cell-based regenerative medicine. Stage-specific embryonic antigen 3 (SSEA3) is a cell surface marker associated with Multilineage-differentiating stress-enduring (Muse) cells, a subpopulation of human bone marrow-derived stem cells (hBMSCs), known for their potent regenerative potential and safety profile. In this study, we investigated the influence of the prolonged culture period and the number of culture passages on the regenerative capacity of hDPSCs and explored the association between SSEA3 expression and their regenerative abilities. Methods hDPSCs were isolated and cultured for up to 20 passages. Cell proliferation, migration, and osteogenic, adipogenic and neurogenic differentiation potential were assessed at passages 5, 10, and 20. Flow cytometry and immunofluorescence were employed to analyze SSEA3 expression. RNA sequencing (RNA-seq) was performed on SSEA3-positive and SSEA3-negative hDPSCs to identify differentially expressed genes and associated pathways. Results Our findings demonstrated a progressive decline in hDPSCs proliferation and migration capacity with increasing passage number. Conversely, cell size exhibited a positive correlation with passage number. Early passage hDPSCs displayed superior osteogenic and adipogenic differentiation potential. Notably, SSEA3 expression exhibited a significant negative correlation with passage numbers, reflecting the observed decline in differentiation capacity. RNA-seq analysis revealed distinct transcriptional profiles between SSEA3-positive and SSEA3-negative hDPSCs. SSEA3-positive cells displayed upregulation of genes associated with ectodermal differentiation and downregulation of genes involved in cell adhesion. Conclusions This study elucidates the impact of passaging on hDPSC behavior and suggests SSEA3 as a valuable biomarker for evaluating stemness and regenerative potential. SSEA3-positive hDPSCs, functionally analogous to Muse cells, represent a promising cell population for developing targeted regenerative therapies with potentially improved clinical outcomes.
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Affiliation(s)
- Jumpei Shirakawa
- Department of Oral and Maxillofacial Surgery, and Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
| | - Edward H. Ntege
- Department of Oral and Maxillofacial Surgery, and Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
| | - Masuo Takemura
- Department of Oral and Maxillofacial Surgery, and Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
| | - Sho Miyamoto
- Department of Oral Surgery, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo, Hokkaido, 060-8543, Japan
| | - Toshihiro Kawano
- Department of Oral and Maxillofacial Surgery, and Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
| | - Chisato Sampei
- Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 287-8510, Japan
| | - Hayato Kawabata
- Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 287-8510, Japan
| | - Hiroyuki Nakamura
- Department of Oral and Maxillofacial Surgery, and Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
| | - Hiroshi Sunami
- Advanced Medical Research Center, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Tadayoshi Hayata
- Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 287-8510, Japan
| | - Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nakagami, Nishihara, Okinawa 903-0215, Japan
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Mizuno M, Yori K, Takeuchi T, Yamamoto T, Ishikawa N, Kobayashi M, Nishio M, Sekiya I. Evaluation of cleaning methods for change-over after the processing of cell products to avoid cross-contamination risk. Regen Ther 2024; 26:489-495. [PMID: 39131505 PMCID: PMC11315063 DOI: 10.1016/j.reth.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 07/04/2024] [Accepted: 07/09/2024] [Indexed: 08/13/2024] Open
Abstract
Introduction Cell-processing facilities face the risk of environmental bacteria contaminating biosafety cabinets during processing, and manual handling of autologous cell products can result in contamination. We propose a risk- and evidence-based cleaning method for cross-contamination, emphasizing proteins and DNA. Methods The transition and residual risks of the culture medium were assessed by measuring both wet and dried media using fluorescence intensity. Residual proteins and DNA in dried culture medium containing HT-1080 cells were analyzed following ultraviolet (UV) irradiation, wiping, and disinfectant treatment. Results Wet conditions showed a higher transition to distilled water (DW), whereas dry conditions led to higher residual amounts on SUS304 plates. Various cleaning methods for residual culture medium were examined, including benzalkonium chloride with a corrosion inhibitor (BKC + I) and DW wiping, which demonstrated significantly lower residual protein and DNA compared to other methods. Furthermore, these cleaning methods were tested for residual medium containing cells, with BKC + I and DW wiping resulting in an undetectable number of cells. However, in some instances, proteins and DNA remained. Conclusions The study compared cleaning methods for proteins and DNA in cell products, revealing their advantages and disadvantages. Peracetic acid (PAA) proved effective for nucleic acids but not proteins, while UV irradiation was ineffective against both proteins and DNA. Wiping emerged as the most effective method, even though traceability remained challenging. However, wiping with ETH was not effective as it caused protein immobilization. Understanding the characteristics of these cleaning methods is crucial for developing effective contamination control strategies.
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Affiliation(s)
- Mitsuru Mizuno
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45, Bunkyo-ku, Yushima, Tokyo 113-8519, Japan
| | - Kouichirou Yori
- Department of HeartSheet Business, Terumo Corporation, 1500 Inokuchi, Nakaicho, Ashigarakami-gun, Kanagawa 259-0151, Japan
| | - Toshikazu Takeuchi
- Department of HeartSheet Business, Terumo Corporation, 1500 Inokuchi, Nakaicho, Ashigarakami-gun, Kanagawa 259-0151, Japan
| | - Takaaki Yamamoto
- Department of HeartSheet Business, Terumo Corporation, 1500 Inokuchi, Nakaicho, Ashigarakami-gun, Kanagawa 259-0151, Japan
| | - Natsumi Ishikawa
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45, Bunkyo-ku, Yushima, Tokyo 113-8519, Japan
| | - Megumi Kobayashi
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45, Bunkyo-ku, Yushima, Tokyo 113-8519, Japan
| | - Miwako Nishio
- Department of Hematology and Biophysical Systems Analysis, Tokyo Medical and Dental University (TMDU), 1-5-45, Bunkyo-ku, Yushima, Tokyo 113-8519, Japan
| | - Ichiro Sekiya
- Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45, Bunkyo-ku, Yushima, Tokyo 113-8519, Japan
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24
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Takahara E, Kamizato K, Kakinohana M, Sunami H, Kise Y, Furukawa K, Ntege EH, Shimizu Y. Subpial transplantation of adipose-derived stem cells alleviates paraplegia in a rat model of aortic occlusion/reperfusion-induced spinal cord infarction. Regen Ther 2024; 26:611-619. [PMID: 39263357 PMCID: PMC11387535 DOI: 10.1016/j.reth.2024.08.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/21/2024] [Accepted: 08/02/2024] [Indexed: 09/13/2024] Open
Abstract
Background Thoracoabdominal periprocedural occlusion/reperfusion injury of the spinal cord (SCII/R) can lead to devastating paraplegia, underscoring the critical need for effective interventions. However, our knowledge of optimal medical strategies and their efficacy remains limited. Preclinical investigations have shown promise in harnessing adult stem cells, including pluripotent and multipotent stem cells such as mesenchymal stem cells (MSCs), to address SCII/R by enhancing neuro-inflammation, axonal growth, and myelination. Particularly, growth factors derived from adipose tissue-derived MSCs (ADSCs) have been proposed to facilitate recovery. Despite advancements, achieving complete recovery remains a formidable challenge. Therefore, gaining a more profound insight into the role of ADSCs in alleviating SCII/R-induced paraplegia, including optimizing the delivery systems for therapies, is imperative. Materials and methods In this study, we assessed the impact of subpial allogeneic rat adipose tissue-derived MSCs (rADSCs) transplantation on paraplegia using a rat SCII/R model induced by ephemeral aortic occlusion, known as the Taira-Marsala model. rADSCs were isolated from adipose tissue of male Sprague-Dawley rats, cultured, characterized, and cryopreserved. One week following the induction of paraplegia, rADSCs (n = 6) or physiological saline (n = 6) were transplanted. Hind limb motor function was evaluated before treatment and at 3-, 7-, and 14-days post-treatment using the Basso-Beattie-Bresnahan scoring system. Results The rADSC-treated group demonstrated a significant improvement in hind limb motor function compared to the saline-treated group (p < 0.05), with 5 out of 6 rats exhibiting enhanced motor function following treatment. Conclusions Our findings suggest that subpial rADSC engraftment may enhance SCII/R-induced paraplegia recovery. These initial results drive further research to validate this potential, understand the molecular mechanisms, and optimize therapies.
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Affiliation(s)
- Eisaku Takahara
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Kota Kamizato
- Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Manabu Kakinohana
- Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Hiroshi Sunami
- Center for Advanced Medical Research, School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Yuya Kise
- Department of Thoracic and Cardiovascular Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Kojiro Furukawa
- Department of Thoracic and Cardiovascular Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Edward Hosea Ntege
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
| | - Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan
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Shimizu Y, Ntege EH, Takahara E, Matsuura N, Matsuura R, Kamizato K, Inoue Y, Sowa Y, Sunami H. Adipose-derived stem cell therapy for spinal cord injuries: Advances, challenges, and future directions. Regen Ther 2024; 26:508-519. [PMID: 39161365 PMCID: PMC11331855 DOI: 10.1016/j.reth.2024.07.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 07/18/2024] [Indexed: 08/21/2024] Open
Abstract
Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions. Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements. Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.
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Affiliation(s)
- Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Edward Hosea Ntege
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Eisaku Takahara
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Naoki Matsuura
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Rikako Matsuura
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Kota Kamizato
- Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Yoshikazu Inoue
- Department of Plastic and Reconstructive Surgery, School of Medicine, Fujita Health University, 1-98, Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192, Japan
| | - Yoshihiro Sowa
- Department of Plastic Surgery, Jichi Medical University, 3311-1, Yakushiji, Shimotsuke, 329-0498, Tochigi, Japan
| | - Hiroshi Sunami
- Center for Advanced Medical Research, School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
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Carmona-Luque MD, Ballesteros-Ribelles A, Millán-López A, Blanco A, Nogueras S, Herrera C. The Effect of Cell Culture Passage on the Efficacy of Mesenchymal Stromal Cells as a Cell Therapy Treatment. J Clin Med 2024; 13:2480. [PMID: 38731011 PMCID: PMC11084414 DOI: 10.3390/jcm13092480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/13/2024] [Accepted: 04/22/2024] [Indexed: 05/13/2024] Open
Abstract
Background/Objective: Mesenchymal Stromal Cells (MSCs) have been considered a promising treatment for several diseases, such as cardiac injuries. Many studies have analyzed their functional properties; however, few studies have characterized MSCs through successive culture passages. The main objective of this work was to analyze the phenotype and functionality of MSCs isolated from two different sources in five culture passages to determine if the culture passage might influence the efficacy of MSCs as a cell therapy treatment. Methods: Bone Marrow (BM)-MSCs were harvested from the femur of Wistar rats (n = 17) and Adipose Tissue(AT)-MSCs were isolated from inguinal fat (n = 17). MSCs were cultured for five culture passages, and the immunophenotype was analyzed by flow cytometry, the functionality was characterized by adipogenic, osteogenic, and chondrogenic differentiation assays, and cytokine secretion capacity was determined through the quantification of the Vascular Endothelial Growth-Factor, Fibroblast Growth-Factor2, and Transforming Growth-Factorβ1 in the cell supernatant. The ultrastructure of MSCs was analyzed by transmission electron microscopy. Results: BM-MSCs exhibited typical phenotypes in culture passages two, four, and five, and their differentiation capacity showed an irregular profile throughout the five culture passages analyzed. AT-MSCs showed a normal phenotype and differentiation capacity in all the culture passages. BM- and AT-MSCs did not modify their secretion ability or ultrastructural morphology. Conclusions: Throughout the culture passages, BM-MSCs, but not AT-MSCs, exhibited changes in their functional and phenotypic characteristic that might affect their efficacy as a cell therapy treatment. Therefore, the culture passage selected should be considered for the application of MSCs as a cell therapy treatment.
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Affiliation(s)
- MDolores Carmona-Luque
- Cell Therapy Group, Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), 14004 Cordoba, Spain; (A.B.-R.); (A.M.-L.); (C.H.)
| | - Antonio Ballesteros-Ribelles
- Cell Therapy Group, Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), 14004 Cordoba, Spain; (A.B.-R.); (A.M.-L.); (C.H.)
| | - Alejandro Millán-López
- Cell Therapy Group, Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), 14004 Cordoba, Spain; (A.B.-R.); (A.M.-L.); (C.H.)
| | - Alfonso Blanco
- Anatomy and Comparative Pathology Department, University of Cordoba, 14014 Cordoba, Spain
| | - Sonia Nogueras
- Cell Therapy Group, Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), 14004 Cordoba, Spain; (A.B.-R.); (A.M.-L.); (C.H.)
| | - Concha Herrera
- Cell Therapy Group, Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), 14004 Cordoba, Spain; (A.B.-R.); (A.M.-L.); (C.H.)
- Department of Hematology, Reina Sofia University Hospital, University of Cordoba, 14014 Cordoba, Spain
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Wang Y, Liu X, Wang B, Sun H, Ren Y, Zhang H. Compounding engineered mesenchymal stem cell-derived exosomes: A potential rescue strategy for retinal degeneration. Biomed Pharmacother 2024; 173:116424. [PMID: 38471273 DOI: 10.1016/j.biopha.2024.116424] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 02/28/2024] [Accepted: 03/08/2024] [Indexed: 03/14/2024] Open
Abstract
The prevalence of retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, has been increasing globally and is linked to the aging population and improved life expectancy. These diseases are characterized by chronic, progressive neuronal damage or depletion of the photoreceptor cells in the retina, and limited effective treatment options are currently available. Mesenchymal stem cell-derived exosomes (MSC-EXOs) containing cytokines, growth factors, lipids, mRNA, and miRNA, which act as mediators of intercellular communication transferring bioactive molecules to recipient cells, offer an appealing, non-cellular nanotherapeutic approach for retinal degenerative diseases. However, treatment specificity is compromised due to their high heterogeneity in size, content, functional effects, and parental cellular source. To improve this, engineered MSC-EXOs with increased drug-loading capacity, targeting ability, and resistance to bodily degradation and elimination have been developed. This review summarizes the recent advances in miRNAs of MSC-EXOs as a treatment for retinal degeneration, discussing the strategies and methods for engineering therapeutic MSC-EXOs. Notably, to address the single functional role of engineered MSC-EXOs, we propose a novel concept called "Compound Engineered MSC-EXOs (Co-E-MSC-EXOs)" along with its derived potential therapeutic approaches. The advantages and challenges of employing Co-E-MSC-EXOs for retinal degeneration in clinical applications, as well as the strategies and issues related to them, are also highlighted.
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Affiliation(s)
- Yao Wang
- Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, the First Affiliated Hospital of Northwest University, Xi'an No.1 hospital, Xi'an, Shaanxi, China; Shaanxi Key Laboratory of Ophthalmology, Shaanxi Institute of Ophthalmology, Xi'an, Shaanxi 710002, China.
| | - Xianning Liu
- Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, the First Affiliated Hospital of Northwest University, Xi'an No.1 hospital, Xi'an, Shaanxi, China; Shaanxi Key Laboratory of Ophthalmology, Shaanxi Institute of Ophthalmology, Xi'an, Shaanxi 710002, China
| | - Bei Wang
- The College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
| | - Hanhan Sun
- The College of Life Sciences, Northwest University, Xi'an, Shaanxi 710069, China
| | - Yiqian Ren
- Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, the First Affiliated Hospital of Northwest University, Xi'an No.1 hospital, Xi'an, Shaanxi, China; Shaanxi Key Laboratory of Ophthalmology, Shaanxi Institute of Ophthalmology, Xi'an, Shaanxi 710002, China
| | - Hongbing Zhang
- Shaanxi Provincial Clinical Research Center for Ophthalmology Diseases, the First Affiliated Hospital of Northwest University, Xi'an No.1 hospital, Xi'an, Shaanxi, China; Shaanxi Key Laboratory of Ophthalmology, Shaanxi Institute of Ophthalmology, Xi'an, Shaanxi 710002, China.
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Zhang J, Suo M, Wang J, Liu X, Huang H, Wang K, Liu X, Sun T, Li Z, Liu J. Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy. Clin Transl Med 2024; 14:e1646. [PMID: 38572666 PMCID: PMC10993161 DOI: 10.1002/ctm2.1646] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2023] [Revised: 02/20/2024] [Accepted: 03/17/2024] [Indexed: 04/05/2024] Open
Abstract
BACKGROUND Stem cell-based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small-scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. METHODS We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. RESULTS We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT-related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. CONCLUSIONS Standardization plays an important role in the sustained, rapid and healthy development of SCT.
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Affiliation(s)
- Jing Zhang
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Moran Suo
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Jinzuo Wang
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Xin Liu
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Huagui Huang
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Kaizhong Wang
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Xiangyan Liu
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Tianze Sun
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
| | - Zhonghai Li
- Department of OrthopedicsFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Key Laboratory of Molecular Mechanism for Repair and Remodeling of Orthopedic DiseasesDalianLiaoning ProvinceChina
- Stem Cell Clinical Research CenterNational Joint Engineering LaboratoryFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Dalian Innovation Institute of Stem Cell and Precision MedicineDalianLiaoning ProvinceChina
| | - Jing Liu
- Stem Cell Clinical Research CenterNational Joint Engineering LaboratoryFirst Affiliated Hospital of Dalian Medical UniversityDalianLiaoning ProvinceChina
- Dalian Innovation Institute of Stem Cell and Precision MedicineDalianLiaoning ProvinceChina
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Humzah D, Molina B, Salti G, Cigni C, Bellia G, Grimolizzi F. Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine? Int J Mol Sci 2024; 25:3216. [PMID: 38542191 PMCID: PMC10970357 DOI: 10.3390/ijms25063216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 02/29/2024] [Accepted: 03/05/2024] [Indexed: 11/11/2024] Open
Abstract
Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.
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Affiliation(s)
- Dalvi Humzah
- Private Practice, West Midlands, Bromsgrove B60 3ET, UK
| | | | | | - Clara Cigni
- IBSA Farmaceutici Italia Srl, 26900 Lodi, Italy
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Takejima AL, Machado-Júnior PAB, Blume GG, Simeoni RB, Francisco JC, Tonial MS, Marqueze LFB, Noronha L, Olandoski M, Abdelwahid E, Carvalho KATDE, Pinho RA, Guarita-Souza LC. Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure. AN ACAD BRAS CIENC 2024; 96:e20230053. [PMID: 38451595 DOI: 10.1590/0001-3765202420230053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 04/19/2023] [Indexed: 03/08/2024] Open
Abstract
Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.
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Affiliation(s)
- Aline L Takejima
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Paulo André B Machado-Júnior
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Gustavo G Blume
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Rossana Baggio Simeoni
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Julio Cesar Francisco
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Murilo S Tonial
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Luis Felipe B Marqueze
- Pontifícia Universidade Católica do Paraná (PUCPR), Laboratory of Exercise Biochemistry in Health, School of Medicine, 1555 Imaculada Conceição Street, Prado Velho, 80215-901 Curitiba, PR, Brazil
| | - Lucia Noronha
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Marcia Olandoski
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
| | - Eltyeb Abdelwahid
- Northwestern University, Feinberg School of Medicine, Feinberg Cardiovascular Research Institute, 303 E. Chicago Ave., Tarry 14-725, 60611 Chicago, IL, USA
| | - Katherine A T DE Carvalho
- The Pelé Pequeno Príncipe Institute, Cell Therapy and Biotechnology in Regenerative Medicine Department, Child and Adolescent Health Research & Pequeno Príncipe Faculties, 1632 Silva Jardim Ave., Água Verde, 80240-020 Curitiba, PR, Brazil
| | - Ricardo A Pinho
- Pontifícia Universidade Católica do Paraná (PUCPR), Laboratory of Exercise Biochemistry in Health, School of Medicine, 1555 Imaculada Conceição Street, Prado Velho, 80215-901 Curitiba, PR, Brazil
| | - Luiz César Guarita-Souza
- Pontifícia Universidade Católica do Paraná (PUCPR), Experimental Laboratory of Institute of Biological and Health Sciences, 1555 Imaculada Conceição Street, 80215-901 Curitiba, PR, Brazil
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Somadder R, Faraj L, Datta S, Kanapathipillai M, Ghosh G. Effect of extracellular matrices on production and potency of mesenchymal stem cell-derived exosomes. Biotechnol J 2024; 19:e2300474. [PMID: 38403471 DOI: 10.1002/biot.202300474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Revised: 12/17/2023] [Accepted: 12/23/2023] [Indexed: 02/27/2024]
Abstract
Mesenchymal stem cell (MSC) derived exosomes have emerged as potential acellular therapeutics for various tissue regenerative applications. However, successful clinical translation of exosome-based therapy is limited by lack of a structured production platform. Thus, in this study, the effect of decellularized extracellular matrix (dECM) was assessed on the production and potency of exosomes secreted by bone marrow-derived human MSCs. The results indicate that there was a ∼2-fold increase in MSC-exosome production when MSCs were cultured on dECM compared to TCP. Further, our study revealed that dECM generation induced by ascorbic acid (AA) up to 100 µg mL-1 highly increased exosome yield thereby indicating a potential scale up method for MSC exosome production. The bioactivity of exosomes was investigated by their ability to improve the healing of wounded human skin explants. Wound closure was enhanced in the presence of exosomes isolated from MSCs cultured on ascorbic acid-induced dECM compared to TCP generated MSC-exosomes. In summary, this study suggests a promising solution to a major bottleneck in large-scale production of MSC exosomes for cell-free therapy.
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Affiliation(s)
- Rittika Somadder
- Bioengineering Program, Department of Mechanical Engineering, University of Michigan-Dearborn, Dearborn, Michigan, USA
| | - Lina Faraj
- Bioengineering Program, Department of Mechanical Engineering, University of Michigan-Dearborn, Dearborn, Michigan, USA
| | - Saurav Datta
- Amgen Bioprocessing Center, Henry E. Riggs School of Applied Life Sciences, Keck Graduate Institute, Claremont, California, USA
| | - Mathumai Kanapathipillai
- Bioengineering Program, Department of Mechanical Engineering, University of Michigan-Dearborn, Dearborn, Michigan, USA
| | - Gargi Ghosh
- Bioengineering Program, Department of Mechanical Engineering, University of Michigan-Dearborn, Dearborn, Michigan, USA
- Amgen Bioprocessing Center, Henry E. Riggs School of Applied Life Sciences, Keck Graduate Institute, Claremont, California, USA
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Santa Cruz-Pavlovich FJ, Bolaños-Chang AJ, Del Rio-Murillo XI, Aranda-Preciado GA, Razura-Ruiz EM, Santos A, Navarro-Partida J. Beyond Vision: An Overview of Regenerative Medicine and Its Current Applications in Ophthalmological Care. Cells 2024; 13:179. [PMID: 38247870 PMCID: PMC10814238 DOI: 10.3390/cells13020179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 12/23/2023] [Accepted: 12/29/2023] [Indexed: 01/23/2024] Open
Abstract
Regenerative medicine (RM) has emerged as a promising and revolutionary solution to address a range of unmet needs in healthcare, including ophthalmology. Moreover, RM takes advantage of the body's innate ability to repair and replace pathologically affected tissues. On the other hand, despite its immense promise, RM faces challenges such as ethical concerns, host-related immune responses, and the need for additional scientific validation, among others. The primary aim of this review is to present a high-level overview of current strategies in the domain of RM (cell therapy, exosomes, scaffolds, in vivo reprogramming, organoids, and interspecies chimerism), centering around the field of ophthalmology. A search conducted on clinicaltrials.gov unveiled a total of at least 209 interventional trials related to RM within the ophthalmological field. Among these trials, there were numerous early-phase studies, including phase I, I/II, II, II/III, and III trials. Many of these studies demonstrate potential in addressing previously challenging and degenerative eye conditions, spanning from posterior segment pathologies like Age-related Macular Degeneration and Retinitis Pigmentosa to anterior structure diseases such as Dry Eye Disease and Limbal Stem Cell Deficiency. Notably, these therapeutic approaches offer tailored solutions specific to the underlying causes of each pathology, thus allowing for the hopeful possibility of bringing forth a treatment for ocular diseases that previously seemed incurable and significantly enhancing patients' quality of life. As advancements in research and technology continue to unfold, future objectives should focus on ensuring the safety and prolonged viability of transplanted cells, devising efficient delivery techniques, etc.
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Affiliation(s)
- Francisco J. Santa Cruz-Pavlovich
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
| | - Andres J. Bolaños-Chang
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
| | - Ximena I. Del Rio-Murillo
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
| | | | - Esmeralda M. Razura-Ruiz
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
| | - Arturo Santos
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
| | - Jose Navarro-Partida
- Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey 64849, Mexico; (F.J.S.C.-P.); (A.J.B.-C.); (X.I.D.R.-M.); (E.M.R.-R.); (A.S.)
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Adamickova A, Chomanicova N, Adamicka M, Valaskova S, Gazova A, Kyselovic J. Isolation and Characterization of Human Dental Pulp Stem Cells Derived from Dental Pulp of Permanent Teeth. Methods Mol Biol 2024; 2835:49-57. [PMID: 39105905 DOI: 10.1007/978-1-0716-3995-5_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
Dental pulp stem cells (DPSCs) are a promising alternative to the source of mesenchymal stem cells (MSCs), as they are readily available in minimally invasive procedures compared to more invasive methods associated with harvesting other MSCs sources. Despite the encouraging pre-clinical outcomes in animal disease models, culture-expanding procedures are needed to obtain a sufficient number of MSCs required for delivery to the damaged site. However, this contributes to increasing regulatory difficulties in translating stem cells and tissue engineering therapy to clinical use. Moreover, discussions continue as to which isolation method is to be preferred when obtaining DPSCs from extracted molars. This protocol describes a simple explant isolation technique of human dental pulp stem cells from the dental pulp of permanent teeth based upon the plastic adherence of MSCs and subsequent outgrowth of cells out of tissue fragments with high efficacy.
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Affiliation(s)
- Adriana Adamickova
- Faculty of Medicine, 5th Department of Internal Medicine, Comenius University Bratislava, Bratislava, Slovakia
| | - Nikola Chomanicova
- International Laser Center, Slovak Centre of Scientifc and Technical Information, Bratislava, Slovakia
| | - Matus Adamicka
- Faculty of Medicine, Institute of Medical Biology, Genetics and Clinical Genetics, Comenius University Bratislava, Bratislava, Slovakia
| | - Simona Valaskova
- International Laser Center, Slovak Centre of Scientifc and Technical Information, Bratislava, Slovakia
| | - Andrea Gazova
- Faculty of Medicine, Institute of Pharmacology and Clinical Pharmacology, Comenius University Bratislava, Bratislava, Slovakia
| | - Jan Kyselovic
- Faculty of Medicine, 5th Department of Internal Medicine, Comenius University Bratislava, Bratislava, Slovakia
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Dhoundiyal S, Alam MA. Advancements in Biotechnology and Stem Cell Therapies for Breast Cancer Patients. Curr Stem Cell Res Ther 2024; 19:1072-1083. [PMID: 37815191 DOI: 10.2174/011574888x268109230924233850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 08/09/2023] [Accepted: 08/18/2023] [Indexed: 10/11/2023]
Abstract
This comprehensive review article examines the integration of biotechnology and stem cell therapy in breast cancer diagnosis and treatment. It discusses the use of biotechnological tools such as liquid biopsies, genomic profiling, and imaging technologies for accurate diagnosis and monitoring of treatment response. Stem cell-based approaches, their role in modeling breast cancer progression, and their potential for breast reconstruction post-mastectomy are explored. The review highlights the importance of personalized treatment strategies that combine biotechnological tools and stem cell therapies. Ethical considerations, challenges in clinical translation, and regulatory frameworks are also addressed. The article concludes by emphasizing the potential of integrating biotechnology and stem cell therapy to improve breast cancer outcomes, highlighting the need for continued research and collaboration in this field.
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Affiliation(s)
- Shivang Dhoundiyal
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar
Pradesh, India
| | - Md Aftab Alam
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar
Pradesh, India
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Abuharb AI, Alzarroug AF, Algahtani SN, Alghamdi HK, Alosaimi FA, Alsuwayna N, Almughira AI. The Impact and Implications of Regenerative Medicine in Urology. Cureus 2024; 16:e52264. [PMID: 38352111 PMCID: PMC10863929 DOI: 10.7759/cureus.52264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2024] [Indexed: 02/16/2024] Open
Abstract
Urology focuses on the treatment of genitourinary disorders through therapies ranging from lifestyle changes to advanced surgeries; the field has recently incorporated robotic and minimally invasive technologies that have improved patient outcomes and reduced hospital stays and complications. However, these methods still have certain limitations. Regenerative medicine, focusing on natural repair abilities, can be an effective and safer alternative. This review aims to examine the impact of regenerative medicine in urology. We adopted a systematic review design by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. An exhaustive online literature search involving the databases PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was conducted spanning the period between January 2010 and October 2023. Data were extracted from studies on regenerative medicine in urology with a special focus on efficacy and safety. Data from 16 studies were analyzed, which showed that cell therapy, biological materials, and tissue engineering are generally used in the field of urinary diseases. The main applications include the regeneration of urinary tissue, the correction of urinary incontinence, the treatment of erectile dysfunction, the reconstruction of ureteric defects, and the formation of bladder tissue. The study findings generally lack definitive conclusions on effectiveness and safety. While our results indicate that regenerative medicine is successful on a subjective level, more clinical trials are needed to establish its effectiveness and safety.
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Affiliation(s)
- Abdullah I Abuharb
- College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU
| | | | - Saad N Algahtani
- College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU
| | - Hatan K Alghamdi
- College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU
| | - Fahad A Alosaimi
- College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU
| | - Nasser Alsuwayna
- College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, SAU
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Smith DK. Supramolecular gels - a panorama of low-molecular-weight gelators from ancient origins to next-generation technologies. SOFT MATTER 2023; 20:10-70. [PMID: 38073497 DOI: 10.1039/d3sm01301d] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/21/2023]
Abstract
Supramolecular gels, self-assembled from low-molecular-weight gelators (LMWGs), have a long history and a bright future. This review provides an overview of these materials, from their use in lubrication and personal care in the ancient world, through to next-generation technologies. In academic terms, colloid scientists in the 19th and early 20th centuries first understood such gels as being physically assembled as a result of weak interactions, combining a solid-like network having a degree of crystalline order with a highly mobile liquid-like phase. During the 20th century, industrial scientists began using these materials in new applications in the polymer, oil and food industries. The advent of supramolecular chemistry in the late 20th century, with its focus on non-covalent interactions and controlled self-assembly, saw the horizons for these materials shifted significantly beyond their historic rheological applications, expanding their potential. The ability to tune the LMWG chemical structure, manipulate hierarchical assembly, develop multi-component systems, and introduce new types of responsive and interactive behaviour, has been transformative. Furthermore, the dynamics of these materials are increasingly understood, creating metastable gels and transiently-fueled systems. New approaches to shaping and patterning gels are providing a unique opportunity for more sophisticated uses. These supramolecular advances are increasingly underpinning and informing next-generation applications - from drug delivery and regenerative medicine to environmental remediation and sustainable energy. In summary, this article presents a panorama over the field of supramolecular gels, emphasising how both academic and industrial scientists are building on the past, and engaging new fundamental insights and innovative concepts to open up exciting horizons for their future use.
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Affiliation(s)
- David K Smith
- Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.
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Barik P, Kuo WW, Kuo CH, Hsieh DJY, Day CH, Daddam J, Chen MYC, Padma VV, Shibu MA, Huang CY. Rewiring of IGF1 secretion and enhanced IGF1R signaling induced by co-chaperone carboxyl-terminus of Hsp70 interacting protein in adipose-derived stem cells provide augmented cardioprotection in aging-hypertensive rats. Aging (Albany NY) 2023; 15:14019-14038. [PMID: 38085649 PMCID: PMC10756089 DOI: 10.18632/aging.205287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 10/04/2023] [Indexed: 12/21/2023]
Abstract
Aging-associated cardiovascular diseases depend on the longitudinal deterioration of stem cell dynamics. The entire mechanism behind it is not completely understood. However, many studies suggest that endocrine pathways, particularly the insulin-like growth factor-1(IGF1) signaling pathway are involved in cardioprotection, especially in stem-cell treatments. Here, we investigated the role of a co-chaperone, carboxyl-terminus of Hsp70 interacting protein (CHIP) in the aspects of growth factor secretion and receptor stabilization in mesenchymal stem cells (MSCs). Briefly, we overexpressed CHIP in rat adipose-derived stem cells (rADSCs) and explored the consequences in vitro, and in vivo, in spontaneously hypertensive rats (SHR). Our data revealed that CHIP overexpression in rADSCs promoted the secretion of insulin-like growth factor-1 (IGF1) and IGF binding protein-3 (IGFBP3) as per immunoblot/cytokine array analysis. We also found that these results were dependent on the nuclear translocation of signal transducer and activator of transcription 3 (STAT3) in rADSCs. Further, the CHIP co-chaperone was also involved in the stabilization of the receptor of IGF1 (IGF1R); interactions between the beta transmembrane region of IGF1R, and the tetracopeptide repeat (TPR) domain of CHIP were evident. Importantly, after the transplantation of lentiviral CHIP overexpression of rADSCs (rADSCsCHIP-WT) into nine months aging-SHR led to an increase in their cardiac function - increased ejection fraction and fractional shortening (≈15% vs. control SHR) - as well as a decrease in their heart size and heart rate, respectively. Altogether, our results support the use of CHIP overexpressing stem cells for the mitigation of cardiac hypertrophy and remodeling associated with late-stage hypertension.
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Affiliation(s)
- Parthasarathi Barik
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Dennis Jine-Yuan Hsieh
- School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan
- Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan
| | | | - Jayasimharayalu Daddam
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
| | | | - V. Vijaya Padma
- Department of Biotechnology, Bharathiar University, Coimbatore, India
| | | | - Chih-Yang Huang
- Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan
- Department of Biotechnology, Asia University, Taichung, Taiwan
- Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan
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Guillaume VGJ, Lanckohr LS, Lippold EF, Beier JP, Ruhl T. Effects of epinephrine, lidocaine, and prilocaine on viability and differentiation capacity of human adipose stem cells. J Plast Reconstr Aesthet Surg 2023; 87:408-415. [PMID: 37939646 DOI: 10.1016/j.bjps.2023.10.104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 10/12/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023]
Abstract
INTRODUCTION Local anesthetics (LAs) are routinely administered in plastic and reconstructive surgery, e.g., as tumescent anesthesia adjunct in liposuction. Historically, these substances were assumed to act cytotoxically. Thus, the application of LA was avoided when handling adipose stem cells (ASCs). We recently determined that most LAs are not cytotoxic when ASCs are exposed to concentrations used for tumescent liposuction. However, there is limited information when combining LA with epinephrine and about the effects of prilocaine on ASCs. METHODS We analyzed the effects of prilocaine or lidocaine in co-exposure with epinephrine on the viability of primary human ASCs, i.e., proliferation, metabolic activity, and cytotoxicity, using crystal violet-staining, PrestoBlue®-, and WST-1 assay. We quantified the impact of short-term incubation of lidocaine and epinephrine on the differentiation of ASCs into the adipogenic, chondrogenic, and osteogenic lineage. RESULTS After 2 h, prilocaine (10 mM) significantly reduced metabolic activity and cell numbers, whereas lidocaine only inhibited metabolic activity. After 6 h, prilocaine (10 mM) and lidocaine significantly decreased metabolic activity as well as cell numbers. The application of high concentrations of epinephrine did not affect cell numbers but diminished metabolic activity. Combining lidocaine with epinephrine had no additional cytotoxic effect. Differentiation into the chondrogenic lineage was significantly inhibited by epinephrine. CONCLUSIONS Deducing from our data, neither lidocaine combined with epinephrine nor prilocaine has a cytotoxic impact on ASCs in vitro at concentrations equivalent to those in tumescent anesthesia and has no long-lasting effect on the differentiation capacity of ASCs into the osteogenic and adipogenic lineage.
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Affiliation(s)
- Vincent G J Guillaume
- Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, NRW, Germany.
| | - Laura S Lanckohr
- Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, NRW, Germany
| | - Ella F Lippold
- Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, NRW, Germany
| | - Justus P Beier
- Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, NRW, Germany
| | - Tim Ruhl
- Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, NRW, Germany
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Russo A, Cortina G, Condello V, Collarile M, Orlandi R, Gianoli R, Giuliani E, Madonna V. Autologous micro-fragmented adipose tissue injection provides significant and prolonged clinical improvement in patients with knee osteoarthritis: a case-series study. J Exp Orthop 2023; 10:116. [PMID: 37968496 PMCID: PMC10651566 DOI: 10.1186/s40634-023-00668-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 10/09/2023] [Indexed: 11/17/2023] Open
Abstract
PURPOSE Among the conservative strategies to manage patients with symptomatic knee osteoarthritis (OA), an innovative approach exploiting the regenerative capability of adipose tissue and its resident MSCs (Mesenchymal Stem Cells or Medicinal Signalling Cells) has been proposed with encouraging results. This study aims to demonstrate the benefits of autologous micro-fragmented adipose tissue (MAT) injection in the conservative treatment of knee osteoarthritis and whether any variables may affect the outcome. This is a case series single-centre study in which patients underwent intraarticular MAT injection without any associated procedures. METHODS Based on inclusion and exclusion criteria, 49 patients (67 Knees) were included and retrospectively analysed with a mean follow-up of 34.04 ± 13.62 months (minimum 11 - maximum 59). Patients were assessed through the WOMAC and KOOS questionnaires at baseline (pre-treatment) and 1-, 3-, 6-, 12-, 24- and 36-month follow-up. A minimal clinically important difference (MCID) of at least 7.5 points for the WOMAC pain scale and 7.2 for the WOMAC function scale compared to the baseline value was used. RESULTS WOMAC and KOOS scores improved after treatment compared to baseline at all follow-ups with p < 0.001. Male gender and Kellgren-Lawrence (KL) grade 2 were associated with smaller improvement in WOMAC and KOOS scores (with respect to females and to KL grade 1, respectively) up to 24 months. The percentage of patients who reach the MCID for WOMAC pain is generally lower than that of patients who reach the MCID for WOMAC function (around 80% at all time points), but it increases significantly over time. Moreover, the baseline score of the WOMAC pain and function influence the outcome. Patients with worse symptoms are more likely to reach the MCID. CONCLUSIONS Intra-articular knee injection of MAT for the treatment of knee osteoarthritis (KOA), recalcitrant to traditional conservative treatments, proved to be effective in a high percentage of cases. The positive association between a worse pre-operative score and a better clinical response to the treatment would support the idea that intra-articular administration of MAT could be considered in patients with very symptomatic KOA in which joint-replacement surgeries are not indicated (or accepted). LEVEL OF EVIDENCE IV, case series.
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Affiliation(s)
- Arcangelo Russo
- Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, Via Mazzini 11, 24128, Bergamo, Italy.
| | - Gabriele Cortina
- Department of Orthopaedic and Trauma Surgery, University Campus Bio-Medico of Rome, 00128, Rome, Italy
| | - Vincenzo Condello
- Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, Via Mazzini 11, 24128, Bergamo, Italy
| | - Marco Collarile
- Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, Via Mazzini 11, 24128, Bergamo, Italy
| | - Roberto Orlandi
- Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, Via Mazzini 11, 24128, Bergamo, Italy
| | - Riccardo Gianoli
- Engineering Department, University of Bergamo, Viale Marconi, 5, 24044, Dalmine, BG, Italy
| | - Emanuele Giuliani
- Engineering Department, University of Bergamo, Viale Marconi, 5, 24044, Dalmine, BG, Italy
| | - Vincenzo Madonna
- Department of Orthopedics, Joint Prosthetic, Arthroscopic Surgery and Sports Traumatology, Humanitas Castelli, Via Mazzini 11, 24128, Bergamo, Italy
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Guillaume VGJ, Lippold EF, Beier JP, Ruhl T. Comprehensive Analysis of Local Anesthetics Affecting Adipose Stem Cells In Vitro. Plast Reconstr Surg 2023; 152:850e-861e. [PMID: 36988627 DOI: 10.1097/prs.0000000000010460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
Abstract
BACKGROUND Adipose stem cells (ASCs) hold a great regenerative capacity because of their differentiation capability and their secretory activity. Thus, ASC survival is of great significance during perioperative harvesting. Various local anesthetics are commonly applied during fat grafting procedures. These substances are known to impair cellular viability, which would affect graft survival and final outcomes, but the exact extent of their impact on ASC biology is unknown. METHODS The authors analyzed the short- and long-term effects of lidocaine, mepivacaine, ropivacaine, and bupivacaine at increasing concentrations (0.1 to 10 mM) on primary human ASC proliferation and metabolic activity. Trilinear differentiation was assessed by oil red O stain (adipogenesis), safranin O (chondrogenesis), and cresolphthalein (osteogenesis) labeling. In supernatants, cytokine [interleukin (IL)-6/IL-8, vascular endothelial growth factor, hepatocyte growth factor] secretion was analyzed by enzyme-linked immunosorbent assay. RESULTS Bupivacaine at greater than 100 µM demonstrated the strongest anti proliferative effects, whereas lidocaine and ropivacaine did not affect cell numbers. Mepivacaine evoked reciprocal results regarding cell count at greater than 1 mM. Each compound impaired trilinear differentiation. Secretion of hepatocyte growth factor and IL-8 was reduced significantly by local anesthetic exposure; levels were restored after substances were washed out. CONCLUSIONS In vitro data show that lidocaine, mepivacaine, and ropivacaine could be applied at concentrations of 1 to 10 mM without affecting ASC survival. In contrast, bupivacaine at concentrations greater than 100 µM should be administered with great caution. The differentiation of ASCs and the ASC's secretome might already be decreased by each local anesthetic at 1 mM. CLINICAL RELEVANCE STATEMENT The authors' experimental data can be of great significance to the clinical practice, as local anesthetics are routinely administered during liposuction as a tumescent anesthesia adjunct. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, V.
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Affiliation(s)
- Vincent G J Guillaume
- From the Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen
| | - Ella F Lippold
- From the Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen
| | - Justus P Beier
- From the Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen
| | - Tim Ruhl
- From the Department of Plastic Surgery, Hand Surgery, Burn Center, University Hospital RWTH Aachen
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Karkehabadi H, Abbasi R, Najafi R, Khoshbin E. The effects of melatonin on the viability and osteogenic/odontogenic differentiation of human stem cells from the apical papilla. Mol Biol Rep 2023; 50:8959-8969. [PMID: 37715020 DOI: 10.1007/s11033-023-08747-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2023] [Accepted: 08/08/2023] [Indexed: 09/17/2023]
Abstract
BACKGROUND An experimental study was conducted to examine whether melatonin influences osteogenic/odontogenic differentiation of human stem cells derived from the apical papilla (hSCAPs). MATERIALS AND METHODS In order to isolate hSCAPs, the undeveloped root of a third molar of a human tooth was used. Melatonin was administered to the experimental groups in an osteogenic medium. No treatment was administered to the control group. The methyl thiazolyl tetrazolium (MTT) assay was performed on days 1, 2, and 3 to assess cell viability (n = 8). A determination of odontogenic/osteogenic differentiation was accomplished using alkaline phosphatase (ALP) activity alizarin red staining (ARS) (n = 6), and the expression of osteogenic genes by real-time polymerase chain reaction (RT-PCR) (n = 3) on days 1, 2, and 7. Evaluation of the data was conducted using SPSS version 18. All experiments were conducted at least three times. The Mann Whitney U test, the ANOVA analysis, Tukey's test, and t-test was implemented to analyze the data (α = 0.05). RESULTS After 24 h, 48 h, and 72 h, No significant difference was observed between the control group and the melatonin treatment group in terms of viability of hSCAPs. (from 1 up to 10 µg/ml) (P > 0.05). The assessment of ARS and ALP activity showed that melatonin treatment enhanced osteogenic differentiation of hSCAPs (P < 0.001). Melatonin treatment caused hSCAPs to show an increase of genes related to osteogenic/odontogenic differentiation. These genes included ALP, dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP-1), and bone sialoprotein (BSP) (P < 0.001). CONCLUSIONS Melatonin treatment enhanced osteogenic/odontogenic differentiation of hSCAPs with a dose dependent effect on cell viability.
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Affiliation(s)
- Hamed Karkehabadi
- Department of Endodontics, Dental Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Roshanak Abbasi
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Rezvan Najafi
- Department of Medical Molecular & Genetics, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Elham Khoshbin
- Department of Endodontics, Dental School, Hamadan University of Medical Sciences, Hamadan, Iran.
- Hamadan Dental School, Shahid Fahmideh Street, PO Box 6517838677, Hamadan, Iran.
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Gysel E, Larijani L, Kallos MS, Krawetz RJ. Suicide gene-enabled cell therapy: A novel approach to scalable human pluripotent stem cell quality control. Bioessays 2023; 45:e2300037. [PMID: 37582645 DOI: 10.1002/bies.202300037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 07/28/2023] [Accepted: 08/02/2023] [Indexed: 08/17/2023]
Abstract
There are an increasing number of cell therapy approaches being studied and employed world-wide. An emerging area in this field is the use of human pluripotent stem cell (hPSC) products for the treatment of injuries/diseases that cannot be effectively managed through current approaches. However, as with any cell therapy, vast numbers of functional and safe cells are required. Bioreactors provide an attractive avenue to generate clinically relevant cell numbers with decreased labour and decreased batch to batch variation. Yet, current methods of performing quality control are not readily scalable to the cell densities produced during bioreactor scale-up. One potential solution is the application of inducible/controllable suicide genes that can trigger cell death in unwanted cell types. These types of approaches have been demonstrated to increase the quality and safety of the resultant cell products. In this review, we will provide background on these approaches and how they could be used together with bioreactor technology to create effective bioprocesses for the generation of high quality and safe hPSCs for use in regenerative medicine approaches.
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Affiliation(s)
- Emilie Gysel
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Biomedical Engineering, University of Calgary, Calgary, AB, Canada
| | - Leila Larijani
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Biomedical Engineering, University of Calgary, Calgary, AB, Canada
| | - Michael S Kallos
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Biomedical Engineering, University of Calgary, Calgary, AB, Canada
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Roman J Krawetz
- McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB, Canada
- Department of Biomedical Engineering, University of Calgary, Calgary, AB, Canada
- Department of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Karimi N. Approaches in line with human physiology to prevent skin aging. Front Physiol 2023; 14:1279371. [PMID: 37954446 PMCID: PMC10634238 DOI: 10.3389/fphys.2023.1279371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Accepted: 10/16/2023] [Indexed: 11/14/2023] Open
Abstract
Skin aging is a complex process that is influenced by intrinsic and extrinsic factors that impact the skin's protective functions and overall health. As the body's outermost layer, the skin plays a critical role in defending it against external threats, regulating body temperature, providing tactile sensation, and synthesizing vitamin D for bone health, immune function, and body homeostasis. However, as individuals age, the skin undergoes structural and functional changes, leading to impairments in these essential functions. In contemporary society, there is an increasing recognition of skin health as a significant indicator of overall wellbeing, resulting in a growing demand for anti-aging products and treatments. However, these products often have limitations in terms of safety, effective skin penetration, and potential systemic complications. To address these concerns, researchers are now focusing on approaches that are safer and better aligned with physiology of the skin. These approaches include adopting a proper diet and maintaining healthy lifestyle habits, the development of topical treatments that synchronize with the skin's circadian rhythm, utilizing endogenous antioxidant molecules, such as melatonin and natural products like polyphenols. Moreover, exploring alternative compounds for sun protection, such as natural ultraviolet (UV)-absorbing compounds, can offer safer options for shielding the skin from harmful radiation. Researchers are currently exploring the potential of adipose-derived stem cells, cell-free blood cell secretome (BCS) and other endogenous compounds for maintaining skin health. These approaches are more secure and more effective alternatives which are in line with human physiology to tackle skin aging. By emphasizing these innovative strategies, it is possible to develop effective treatments that not only slow down the skin aging process but also align better with the natural physiology of the skin. This review will focus on recent research in this field, highlighting the potential of these treatments as being safer and more in line with the skin's physiology in order to combat the signs of aging.
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Affiliation(s)
- Nazli Karimi
- Department of Physiology, Faculty of Medicine, Hacettepe University, Ankara, Türkiye
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Adriansyah RF, Margiana R, Supardi S, Narulita P. Current Progress in Stem Cell Therapy for Male Infertility. Stem Cell Rev Rep 2023; 19:2073-2093. [PMID: 37440145 DOI: 10.1007/s12015-023-10577-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/14/2023] [Indexed: 07/14/2023]
Abstract
Infertility has become one of the most common issues worldwide, which has negatively affected society and infertile couples. Meanwhile, male infertility is responsible for about 50% of infertility. Accordingly, a great number of researchers have focused on its treatment during the last few years; however, current therapies such as assisted reproductive technology (ART) are not effective enough in treating male infertility. Because of their self-renewal and differentiation capabilities and unlimited sources, stem cells have recently raised great hope in the treatment of reproductive system disorders. Stem cells are undifferentiated cells that can induce different numbers of specific cells, such as male and female gametes, demonstrating their potential application in the treatment of infertility. The present review aimed at identifying the causes and potential factors that influence male fertility. Besides, we highlighted the recent studies that investigated the efficiency of stem cells such as spermatogonial stem cells (SSCs), embryonic stem cells (ESCs), very small embryonic-like stem cells (VSELs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) in the treatment of various types of male infertility.
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Affiliation(s)
| | - Ria Margiana
- Andrology Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.
- Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.
- Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
- Master's Programme Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
- Indonesia General Academic Hospital, Depok, Indonesia.
- Ciptomangunkusumo General Academic Hospital, Jakarta, Indonesia.
| | - Supardi Supardi
- Andrology Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Pety Narulita
- Andrology Program, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
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Gholami Farashah MS, Mohammadi A, Javadi M, Soleimani Rad J, Shakouri SK, Meshgi S, Roshangar L. Bone marrow mesenchymal stem cells' osteogenic potential: superiority or non-superiority to other sources of mesenchymal stem cells? Cell Tissue Bank 2023; 24:663-681. [PMID: 36622494 DOI: 10.1007/s10561-022-10066-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 12/14/2022] [Indexed: 01/10/2023]
Abstract
Skeletal problems are an increasing issue due to the increase in the global aging population. Different statistics reports show that today, the global population is aging that results in skeletal problems, increased health system costs, and even higher mortality associated with skeletal problems. Common treatments such as surgery and bone grafts are not always effective and in some cases, they can even cause secondary problems such as infections or improper repair. Cell therapy is a method that can be utilized along with common treatments independently. Mesenchymal stem cells (MSCs) are a very important and efficient source in terms of different diseases, especially bone problems. These cells are present in different tissues such as bone marrow, adipose tissue, umbilical cord, placenta, dental pulp, peripheral blood, amniotic fluid and others. Among the types of MSCs, bone marrow mesenchymal stem cells (BMMSCs) are the most widely used source of these cells, which have appeared to be very effective and promising in terms of skeletal diseases, especially compared to the other sources of MSCs. This study focuses on the specific potential and content of BMMSCs from which the specific capacity of these cells originates, and compares their osteogenic potential with other types of MSCs, and also the future directions in the application of BMMSCs as a source for cell therapy.
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Affiliation(s)
- Mohammad Sadegh Gholami Farashah
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amirhossein Mohammadi
- Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Javadi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jafar Soleimani Rad
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Kazem Shakouri
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahla Meshgi
- Cardiovascular Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Leila Roshangar
- Physical Medicine and Rehabilitation Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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Shimizu Y, Ntege EH, Azuma C, Uehara F, Toma T, Higa K, Yabiku H, Matsuura N, Inoue Y, Sunami H. Management of Rheumatoid Arthritis: Possibilities and Challenges of Mesenchymal Stromal/Stem Cell-Based Therapies. Cells 2023; 12:1905. [PMID: 37508569 PMCID: PMC10378234 DOI: 10.3390/cells12141905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2023] [Revised: 06/28/2023] [Accepted: 07/14/2023] [Indexed: 07/30/2023] Open
Abstract
Rheumatoid arthritis (RA) is a highly prevalent, chronic, and progressive autoimmune disorder primarily affecting joints and muscles. The associated inflammation, pain, and motor restriction negatively impact patient quality of life (QOL) and can even contribute to premature mortality. Further, conventional treatments such as antiinflammatory drugs are only symptomatic. Substantial progress has been made on elucidating the etiopathology of overt RA, in particular the contributions of innate and adaptive immune system dysfunction to chronic inflammation. Although the precise mechanisms underlying onset and progression remain elusive, the discovery of new drug targets, early diagnosis, and new targeted treatments have greatly improved the prognosis and QOL of patients with RA. However, a sizable proportion of patients develop severe adverse effects, exhibit poor responses, or cannot tolerate long-term use of these drugs, necessitating more effective and safer therapeutic alternatives. Mounting preclinical and clinical evidence suggests that the transplantation of multipotent adult stem cells such as mesenchymal stromal/stem cells is a safe and effective treatment strategy for controlling chronic inflammation and promoting tissue regeneration in patients with intractable diseases, including RA. This review describes the current status of MSC-based therapies for RA as well as the opportunities and challenges to broader clinical application.
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Affiliation(s)
- Yusuke Shimizu
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Edward Hosea Ntege
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Chinatsu Azuma
- Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Fuminari Uehara
- Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Takashi Toma
- Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Kotaro Higa
- Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Hiroki Yabiku
- Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Naoki Matsuura
- Department of Plastic and Reconstructive Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
| | - Yoshikazu Inoue
- Department of Plastic and Reconstructive Surgery, School of Medicine, Fujita Health University, Toyoake 470-1192, Japan
| | - Hiroshi Sunami
- Center for Advanced Medical Research, School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan
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Kim S, Kang GH, Lim KM, Shin Y, Song K, Park S, An J, Kim DY, Shin HC, Cho SG. Thermostable Human Basic Fibroblast Growth Factor (TS-bFGF) Engineered with a Disulfide Bond Demonstrates Superior Culture Outcomes in Human Pluripotent Stem Cell. BIOLOGY 2023; 12:888. [PMID: 37372172 DOI: 10.3390/biology12060888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/14/2023] [Accepted: 06/18/2023] [Indexed: 06/29/2023]
Abstract
Human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) can differentiate into various tissues and are an essential source of various disease models and therapeutics. Various growth factors are required in order to culture pluripotent stem cells, among which basic fibroblast growth factor (bFGF) is essential for maintaining stem cell ability. However, bFGF has a short half-life (8 h) under normal mammalian cell culture conditions, and its activity decreases after 72 h, posing a serious problem in the production of high-quality stem cells. Here, we evaluated the various functions of pluripotent stem cells (PSCs) by utilizing an engineered thermostable bFGF (TS-bFGF) that is thermally stable and maintains activity longer under mammalian culture conditions. PSCs cultured with TS-bFGF showed better proliferation, stemness, morphology, and differentiation than cells cultured with wild-type bFGF. In light of the importance of stem cells in a wide range of applications in the medical and biotechnology fields, we anticipate that TS-bFGF, as a thermostable and long-acting bFGF, can play a key role in securing high-quality stem cells through various sets of stem cell culture processes.
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Affiliation(s)
- Sejong Kim
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Geun-Ho Kang
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Kyung Min Lim
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Yeokyung Shin
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Kwonwoo Song
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Sangrok Park
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Jongyub An
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
| | - Dae Young Kim
- PnP Biopharm Co., Ltd., 1304, Acetechnotower 8-cha, 11 Digital-ro 33-gil, Guro-gu, Seoul 08380, Republic of Korea
| | - Hang-Cheol Shin
- PnP Biopharm Co., Ltd., 1304, Acetechnotower 8-cha, 11 Digital-ro 33-gil, Guro-gu, Seoul 08380, Republic of Korea
| | - Ssang-Goo Cho
- Department of Stem Cell and Regenerative Biotechnology, Molecular & Cellular Reprogramming Center and Institute of Advanced Regenerative Science, Konkuk University, 120 Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
- R&D Team, StemExOne Co., Ltd., 307 KU Technology Innovation Bldg, 120, Neungdong-ro Gwangjin-gu, Seoul 05029, Republic of Korea
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Stage HJ, Trappe S, Söllig K, Trachsel DS, Kirsch K, Zieger C, Merle R, Aschenbach JR, Gehlen H. Multilineage Differentiation Potential of Equine Adipose-Derived Stromal/Stem Cells from Different Sources. Animals (Basel) 2023; 13:ani13081352. [PMID: 37106915 PMCID: PMC10135324 DOI: 10.3390/ani13081352] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/06/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
The investigation of multipotent stem/stromal cells (MSCs) in vitro represents an important basis for translational studies in large animal models. The study's aim was to examine and compare clinically relevant in vitro properties of equine MSCs, which were isolated from abdominal (abd), retrobulbar (rb) and subcutaneous (sc) adipose tissue by collagenase digestion (ASCs-SVF) and an explant technique (ASCs-EXP). Firstly, we examined proliferation and trilineage differentiation and, secondly, the cardiomyogenic differentiation potential using activin A, bone morphogenetic protein-4 and Dickkopf-1. Fibroblast-like, plastic-adherent ASCs-SVF and ASCs-EXP were obtained from all sources. The proliferation and chondrogenic differentiation potential did not differ significantly between the isolation methods and localizations. However, abd-ASCs-EXP showed the highest adipogenic differentiation potential compared to rb- and sc-ASCs-EXP on day 7 and abd-ASCs-SVF a higher adipogenic potential compared to abd-ASCs-EXP on day 14. Osteogenic differentiation potential was comparable at day 14, but by day 21, abd-ASCs-EXP demonstrated a higher osteogenic potential compared to abd-ASCs-SVF and rb-ASCs-EXP. Cardiomyogenic differentiation could not be achieved. This study provides insight into the proliferation and multilineage differentiation potential of equine ASCs and is expected to provide a basis for future preclinical and clinical studies in horses.
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Affiliation(s)
- Hannah J Stage
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Susanne Trappe
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Katharina Söllig
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Dagmar S Trachsel
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria
| | - Katharina Kirsch
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Cornelia Zieger
- Institute of Veterinary Pathology Department of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany
| | - Roswitha Merle
- Institute for Veterinary Epidemiology and Biostatistics, Department of Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany
| | - Jörg R Aschenbach
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Heidrun Gehlen
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
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Hosseini M, Shafiee A. Vascularization of cutaneous wounds by stem cells. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 199:327-350. [PMID: 37678977 DOI: 10.1016/bs.pmbts.2023.03.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2023]
Abstract
Differentiated skin cells have limited self-renewal capacity; thus, the application of stem/progenitor cells, adult or induced stem cells, has attracted much attention for wound healing applications. Upon skin injury, vascularization, known as a highly dynamic process, occurs with the contribution of cells, the extracellular matrix, and relevant growth factors. Considering the importance of this process in tissue regeneration, several strategies have been proposed to enhance angiogenesis and accelerate wound healing. Previous studies report the effectiveness of stem/progenitor cells in skin wound healing by facilitating the vascularization process. This chapter reviews and highlights some of the key and recent investigations on application of stem/progenitor cells to induce skin revascularization after trauma.
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Affiliation(s)
- Motaharesadat Hosseini
- School of Mechanical, Medical and Process Engineering, Faculty of Engineering, Queensland University of Technology, Brisbane, QLD, Australia; ARC Industrial Transformation Training Centre for Multiscale 3D Imaging, Modelling and Manufacturing (M3D), Queensland University of Technology, Brisbane, QLD, Australia
| | - Abbas Shafiee
- Herston Biofabrication Institute, Metro North Hospital and Health Service, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service, Brisbane, QLD, Australia; Frazer Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
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A Simplified and Effective Approach for the Isolation of Small Pluripotent Stem Cells Derived from Human Peripheral Blood. Biomedicines 2023; 11:biomedicines11030787. [PMID: 36979766 PMCID: PMC10045871 DOI: 10.3390/biomedicines11030787] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Revised: 02/24/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
Pluripotent stem cells are key players in regenerative medicine. Embryonic pluripotent stem cells, despite their significant advantages, are associated with limitations such as their inadequate availability and the ethical dilemmas in their isolation and clinical use. The discovery of very small embryonic-like (VSEL) stem cells addressed the aforementioned limitations, but their isolation technique remains a challenge due to their small cell size and their efficiency in isolation. Here, we report a simplified and effective approach for the isolation of small pluripotent stem cells derived from human peripheral blood. Our approach results in a high yield of small blood stem cell (SBSC) population, which expresses pluripotent embryonic markers (e.g., Nanog, SSEA-3) and the Yamanaka factors. Further, a fraction of SBSCs also co-express hematopoietic markers (e.g., CD45 and CD90) and/or mesenchymal markers (e.g., CD29, CD105 and PTH1R), suggesting a mixed stem cell population. Finally, quantitative proteomic profiling reveals that SBSCs contain various stem cell markers (CD9, ITGA6, MAPK1, MTHFD1, STAT3, HSPB1, HSPA4), and Transcription reg complex factors (e.g., STAT5B, PDLIM1, ANXA2, ATF6, CAMK1). In conclusion, we present a novel, simplified and effective isolating process that yields an abundant population of small-sized cells with characteristics of pluripotency from human peripheral blood.
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