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Gupta A, Ghosh A, Sharma N, Gorain B. Advancements in Stem Cell Research for Effective Therapies Against Alzheimer's Disease: Current Investigation and Future Insight. Mol Neurobiol 2025:10.1007/s12035-025-05003-3. [PMID: 40327307 DOI: 10.1007/s12035-025-05003-3] [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: 09/29/2024] [Accepted: 04/25/2025] [Indexed: 05/07/2025]
Abstract
Alzheimer's disease (AD) is the most prevalent cause of dementia in the elderly, affecting approximately 50 million individuals globally with significant impose in health and financial burdens. Despite extensive research, no current treatment effectively halts the progression of AD, primarily due to its complex pathophysiology of the disease and the limitations of available therapeutic approaches. In this context, stem cell transplantation has emerged as a promising treatment strategy, harnessing the regenerative capabilities of various stem cell types, including neural stem cells (NSCs), embryonic stem cells (ESCs), and mesenchymal stem cells (MSCs). This review explores the potential of stem cell-based therapies in AD, emphasizing the necessity for continued innovation to overcome existing challenges and enhance therapeutic efficacy. Briefly, NSCs have shown potential in improving cognitive function and reducing AD pathology through targeted transplantation and neuroprotection; however, challenges such as optimizing transplantation protocols and ensuring effective cell integration persist. Concurrently, ESCs, with their pluripotent nature, present opportunities for modulating AD and generating therapeutic neurons, but ethical concerns and immunogenicity present significant obstacles to clinical application. Moreover, MSCs have demonstrated potential in ameliorating AD-related pathology and promoting neurogenesis, offering a more accessible alternative with fewer ethical constraints. The review concludes that the combinatory approaches of different stem cells may provide synergistic benefits in addressing AD-related pathophysiology, warranting further exploration in future research.
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Affiliation(s)
- Abhinav Gupta
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
| | - Arya Ghosh
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
| | - Neelima Sharma
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India
| | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
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2
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Goff AD, Zhang X, Thomas B, Ong SSY, Atala A, Zhang Y. Body Fluid-Derived Stem Cells: Powering Innovative, Less-Invasive Cell Therapies. Int J Mol Sci 2025; 26:4382. [PMID: 40362618 DOI: 10.3390/ijms26094382] [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: 04/01/2025] [Revised: 05/02/2025] [Accepted: 05/02/2025] [Indexed: 05/15/2025] Open
Abstract
Stem cell therapy offers significant promise for tissue regeneration and repair. Traditionally, bone marrow- and adipose-derived stem cells have served as primary sources, but their clinical use is limited by invasiveness and low cell yield. This review focuses on body fluid-derived stem cells as an emerging, non-invasive, and readily accessible alternative. We examine stem cells isolated from amniotic fluid, peripheral blood, cord blood, menstrual fluid, urine, synovial fluid, breast milk, and cerebrospinal fluid, highlighting their unique biological properties and therapeutic potential. By comparing their characteristics and barriers to clinical translation, we propose body fluid-derived stem cells as a promising source for regenerative applications, with continued research needed to fully achieve their clinical utility.
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Affiliation(s)
- Adam David Goff
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
- School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Xinyue Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Biju Thomas
- Keck School of Medicine of USC, University of Southern California, Los Angeles, CA 90033, USA
| | - Sally Shin Yee Ong
- Department of Ophthalmology, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Anthony Atala
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
| | - Yuanyuan Zhang
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC 27101, USA
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3
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Shao M, Rahmdel M, Shayan SK, Hassannia E, Khedmatgozar M, Yousefi K, Ali-Khiavi P, Hjazi A, Al-Aouadi RFA, Sarvestani PA, Fard MRG, Nourizadeh M, Khiabani SS, Suliman M, Nataj PG, Hamzehzadeh S. Advancements in Biomaterials for Stem Cell Differentiation. Stem Cell Rev Rep 2025:10.1007/s12015-025-10879-8. [PMID: 40257542 DOI: 10.1007/s12015-025-10879-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/04/2025] [Indexed: 04/22/2025]
Abstract
The field of regenerative medicine has witnessed significant advancements in recent years, particularly in the application of biomaterials to enhance stem cell differentiation. Biomaterials serve as scaffolds that can support cellular functions and influence the fate of stem cells through biochemical and physical cues. This paper reviews recent advancements in biomaterials designed for stem cell differentiation, focusing on their composition, properties, and applications in tissue engineering. We explore various types of biomaterials, including natural polymers, synthetic polymers, hydrogels, and nanomaterials, and discuss how they can be tailored to create microenvironments that promote specific differentiation pathways. Additionally, we highlight the challenges and future directions in this rapidly evolving field.
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Affiliation(s)
- Mingchen Shao
- Department of Cardiovascular Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), 119991, Moscow, Russian Federation
| | - Mohamad Rahmdel
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Sepideh Karkon Shayan
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Elham Hassannia
- Student Research Commitee, School of Medicine, Kerman University of Medical Ssciences, Kerman, Iran
| | | | - Khadije Yousefi
- Department of Materials Science and Engineering, School of Engineering, Yasouj University, Yasouj, Iran
| | - Payam Ali-Khiavi
- Student Research Commitee, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahmed Hjazi
- Department of Medical Laboratory, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, 11942, Al-Kharj, Saudi Arabia
| | | | - Paria Arjmandi Sarvestani
- Department of Biomedical Engineering, Faculty of Engineering, Zand Institute of Higher Education, Shiraz, Iran
| | | | - Mehrdad Nourizadeh
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Muath Suliman
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, 61413, Abha, Saudi Arabia
| | | | - Sina Hamzehzadeh
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
- Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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4
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Lee EJ, Sun R, Kim J. The self-renewal function of Oct-4 can be replaced by the EWS-Oct-4 fusion protein in embryonic stem cells. Cell Mol Life Sci 2025; 82:166. [PMID: 40251420 PMCID: PMC12008092 DOI: 10.1007/s00018-025-05701-0] [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: 11/26/2024] [Revised: 03/31/2025] [Accepted: 04/07/2025] [Indexed: 04/20/2025]
Abstract
Octamer-binding transcription factor 4 (Oct-4) is essential for maintenance and pluripotency of embryonic stem (ES) cells. Despite the structural similarities between Oct-4 and its homologs (Oct-1, Oct-2, and Oct-6), these homologs cannot serve as substitutes for Oct-4 when generating stem cell colonies. While nuclear receptor subfamily 5, group A, member 2 (Nr5a2) can temporarily serve as a substitute for Oct-4 during cellular reprogramming, it is insufficient to maintain these functions in ES cells. The EWS-Oct-4 fusion protein, which was identified in human tumors, is a viable alternative that can potentially sustain and enhance ES cell functions. This study used ZHBTc4 ES cells, which have tetracycline-regulated Oct-4 expression, to explore the capabilities of EWS-Oct-4. It employed a variety of assays, including western blotting, immunocytochemistry, RT-PCR, luciferase reporter assays, flow cytometry, and teratoma formation assays. EWS-Oct-4 preserved the self-renewal capacity of Oct-4-null ES cells, as demonstrated by their undifferentiated morphology and increased expression of pluripotency markers such as Sox2, Nanog, and SSEA-1. It also boosted cell proliferation and influenced cell cycle dynamics by downregulating p21 and upregulating Oct-4 target genes, including Rex-1 and fibroblast growth factor-4. Epithelial markers were upregulated and mesenchymal markers were downregulated, suggesting a shift toward an epithelial phenotype. Prominent teratoma formation further confirmed the functionality of EWS-Oct-4 in vivo. The integrity and specific functional domains of EWS-Oct-4 were critical for these effects. Finally, comparative transcriptomic analysis revealed that ES cells expressing EWS-Oct-4 and those expressing Oct-4 had highly similar global gene expression profiles, with distinct variations in differentially expressed genes. These findings indicate that EWS-Oct-4 can effectively replace Oct-4, which has significant implications for advancements in stem cell research and regenerative medicine.
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Affiliation(s)
- Eun Joo Lee
- Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea
| | - Ruijing Sun
- Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea
| | - Jungho Kim
- Laboratory of Molecular and Cellular Biology, Department of Life Science, Sogang University, Seoul, 04107, Korea.
- Stress-Responding Bionanomaterial Center, Sogang University, Seoul, 04107, Korea.
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Bakr MM, Al Ankily M, Shamel M. The Protective Effects of MSC-Derived Exosomes Against Chemotherapy-Induced Parotid Gland Cytotoxicity. Int J Dent 2025; 2025:5517092. [PMID: 40223864 PMCID: PMC11986938 DOI: 10.1155/ijod/5517092] [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: 01/08/2025] [Accepted: 03/13/2025] [Indexed: 04/15/2025] Open
Abstract
Background: Fluorouracil (5-FU) is one of the most popular chemotherapeutic agents used in various cancer therapy protocols. Cell-free therapy utilizing exosomes is gaining increased popularity as a safer option due to concerns over potential tumor progression following stem cell therapy. Methods: Parotid glands of albino were treated with a single bone marrow mesenchymal stem cell (BMMSC)-derived exosomes injection (100 μg/kg/dose suspended in 0.2 mL phosphate-buffered saline [PBS]), a single 5-Fu injection (20 mg/kg), and BMMSC-derived exosomes plus 5-FU and compared to control group (daily saline injections). After 30 days, the parotid glands were examined using qualitative histological evaluation, immunohistochemical evaluation using rabbit polyclonal mouse antibody to Ki-67, caspase 3, and iNOS, as well as quantitative real-time polymerase chain reaction (RT-PCR) to evaluate gene expression of TGFβ1, TNF-α, and BCL-2. Results: Histological examination of the parotid gland revealed that BMMSC-derived exosomes restored the glands' architecture and repaired most of the distortion created by 5-FU. Immunohistochemical expression of tumor proliferation and cell death markers were restored to normal levels in the exosome-treated groups that were similar to the control group. Furthermore, BMMSC-derived exosomes reversed the effects of 5-FU on quantitative gene expression levels and showed a significant decrease in TNF-α (p < 0.001) and a significant increase in TGFβ (p < 0.0001) and BCL-2 (p < 0.05) when compared to 5-FU treatment. Conclusion: Within the limitations of the current study, BMMSC-derived exosomes have the potential to counteract the cytotoxic effects of 5-FU on the parotid glands of rats in vivo. Further studies are deemed necessary to simulate clinical scenarios.
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Affiliation(s)
- Mahmoud M. Bakr
- General Dental Practice, School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland 4215, Australia
| | - Mahmoud Al Ankily
- Faculty of Dentistry, Oral Biology Department, The British University in Egypt, Cairo, Egypt
| | - Mohamed Shamel
- Faculty of Dentistry, Oral Biology Department, The British University in Egypt, Cairo, Egypt
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Narasimha RB, Shreya S, Jayabal VA, Yadav V, Rath PK, Mishra BP, Kancharla S, Kolli P, Mandadapu G, Kumar S, Mohanty AK, Jena MK. Stem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review. Vet Sci 2025; 12:67. [PMID: 39852942 PMCID: PMC11768649 DOI: 10.3390/vetsci12010067] [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: 12/04/2024] [Revised: 01/03/2025] [Accepted: 01/13/2025] [Indexed: 01/26/2025] Open
Abstract
Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases. Although there are substantial studies revealing the treatment of human degenerative diseases using stem cells, this is yet to be explored in livestock animals. Many diseases in livestock species such as mastitis, laminitis, neuromuscular disorders, autoimmune diseases, and some debilitating diseases are not covered completely by the existing drugs and treatment can be improved by using different types of stem cells like embryonic stem cells, adult stem cells, and induced pluripotent stem cells. This review mainly focuses on the use of stem cells for disease treatment in livestock animals. In addition to the diseases mentioned, the potential of stem cells can be helpful in wound healing, skin disease therapy, and treatment of some genetic disorders. This article explores the potential of stem cells from various sources in the therapy of livestock diseases and also their role in the conservation of endangered species as well as disease model preparation. Moreover, the future perspectives and challenges associated with the application of stem cells in livestock are discussed. Overall, the transformative impact of stem cell research on the livestock sector is comprehensively studied which will help researchers to design future research work on stem cells related to livestock diseases.
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Affiliation(s)
- Raghavendra B. Narasimha
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India; (R.B.N.); (S.S.)
| | - Singireddy Shreya
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India; (R.B.N.); (S.S.)
| | - Vijay Anand Jayabal
- Department of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai 600051, Tamil Nadu, India;
| | - Vikas Yadav
- Department of Clinical Sciences, Clinical Research Centre, Skåne University Hospital, Lund University, SE 20213 Malmö, Sweden
| | - Prasana Kumar Rath
- College of Veterinary Science and AH, Odisha University of Agriculture and Technology, Bhubaneswar 751003, Odisha, India; (P.K.R.); (B.P.M.)
| | - Bidyut Prava Mishra
- College of Veterinary Science and AH, Odisha University of Agriculture and Technology, Bhubaneswar 751003, Odisha, India; (P.K.R.); (B.P.M.)
| | - Sudhakar Kancharla
- Devansh Lab Werks, 234 Aquarius Drive, Homewood, AL 35209, USA; (S.K.); (G.M.)
| | - Prachetha Kolli
- Microgen Health Inc., 14225 Sullyfield Cir Suite E, Chantilly, VA 20151, USA;
| | - Gowtham Mandadapu
- Devansh Lab Werks, 234 Aquarius Drive, Homewood, AL 35209, USA; (S.K.); (G.M.)
| | - Sudarshan Kumar
- Cell, Molecular and Proteomics Lab, Animal Biotechnology Centre, ICAR-National Dairy Research Institute (ICAR-NDRI), Karnal 132001, Haryana, India;
| | - Ashok Kumar Mohanty
- ICAR-Central Institute for Research on Cattle (ICAR-CIRC), Meerut 250001, Uttar Pradesh, India;
| | - Manoj Kumar Jena
- Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara 144411, Punjab, India; (R.B.N.); (S.S.)
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Sueters J, van Heiningen R, de Vries R, Guler Z, Huirne J, Smit T. Advances in tissue engineering of peripheral nerve and tissue innervation - a systematic review. J Tissue Eng 2025; 16:20417314251316918. [PMID: 39911939 PMCID: PMC11795627 DOI: 10.1177/20417314251316918] [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: 09/10/2024] [Accepted: 01/15/2025] [Indexed: 02/07/2025] Open
Abstract
Although various options are available to treat injured organs and peripheral nerves, none is without limitations. Auto- and allografts are the first choice of treatment, but tissue survival or functionality is not guaranteed due to often limited vascular and neural networks. In response, tissue-engineered solutions have been developed, yet clinical translations is rare. In this study, a systematic review was performed on tissue-engineered advancements for peripheral nerves and tissues, to aid future developments in bridging the gap toward the clinic by identifying high-potential solutions and unexplored areas. A systematic search was performed in PubMed, Embase, Web of Science, and Scopus until November 9, 2023. Search terms involved "tissue engineering," "guided," "tissue scaffold," and "tissue graft," together with "innervation" and "reinnervation." Original in vivo or in vitro studies meeting the inclusion criteria (tissue-engineered peripheral nerve/innervation of tissue) and no exclusion criteria (no full text available; written in foreign language; nonoriginal article; tissue-engineering of central nervous system; publication before 2012; insufficient study quality or reproducibility) were assessed. A total of 68 out of 3626 original studies were included. Data extraction was based on disease model, cell origin and host species, biomaterial nature and composition, and external stimuli of biological, chemical or physical origin. Although tissue engineering is still in its infancy, explored innervation strategies of today were highlighted with respect to biomaterials, cell types, and external stimuli. The findings emphasize that natural biomaterials, pre-seeding with autologous cell sources, and solutions for reproductive organs are beneficial for future research. Natural biomaterials possess important cues required for cell-material interaction and closely resemble native tissue in terms of biomechanical, geometrical and chemical composition. Autologous cells induce biomaterial functionalization. As these solutions pose no risk of immunorejection and have demonstrated good outcomes, they are most likely to fulfill the clinical demands.
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Affiliation(s)
- Jayson Sueters
- Department of Gynaecology, Amsterdam UMC – location VUmc, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
| | - Rowan van Heiningen
- Department of Gynaecology, Amsterdam UMC – location VUmc, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
- Angiogenesis Laboratory, Cancer Center Amsterdam, Department of Medical Oncology, Amsterdam UMC – location VUmc, Amsterdam, The Netherlands
| | - Ralph de Vries
- Medical Library, Vrije Universiteit, Amsterdam, The Netherlands
| | - Zeliha Guler
- Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
- Department of Obstetrics and Gynecology, Amsterdam UMC – location AMC, Amsterdam, The Netherlands
| | - Judith Huirne
- Department of Gynaecology, Amsterdam UMC – location VUmc, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
| | - Theo Smit
- Department of Gynaecology, Amsterdam UMC – location VUmc, Amsterdam, The Netherlands
- Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
- Department of Medical Biology, Amsterdam UMC – location AMC, Amsterdam, The Netherlands
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González-Gil A, Sánchez-Maldonado B, Sánchez Pérez Á, Aranda PJ, Picazo RA. Cell Population Analyses of Neurospheres Generated In Vitro from Ovarian Cortical Cells in Mammals: Characterization by Immunohistochemistry and Flow Cytometry. Methods Mol Biol 2025; 2899:289-307. [PMID: 40067632 DOI: 10.1007/978-1-0716-4386-0_20] [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: 05/13/2025]
Abstract
Alternative experimental models based upon isolation and culture of extra-neural NSC/NPC or adult stem cells that can be induced in vitro to generate these cells and NS rely on development of procedures that can demonstrate the identity of cells as NSC/NPC and their compromise with the neural lineage during culture. Gene expression analyses by RT-PCRQ, immunohistochemical localization of characteristic NSC/NPC antigens, analyses of cell populations by flow cytometry, or ultrastructural analyses of in vitro generated NS are the most frequent and reliable methods to demonstrate the molecular and structural hallmarks of NSC/NPCs and NS. Among all these techniques, those aimed to immunolocalize specific NSC/NPC antigens on a cell basis and in a time-dependent fashion throughout culture require skillful NS processing before setting up the technique. In this chapter, comprehensive protocols for grouped OCC-NS preaggregation and paraffin embedding for immunolocalization of NSC/NPC antigens and NS population analyses by flow cytometry are fully explained.
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Affiliation(s)
- Alfredo González-Gil
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Belén Sánchez-Maldonado
- Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Ángeles Sánchez Pérez
- Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Pedro José Aranda
- Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
| | - Rosa Ana Picazo
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain.
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Kang D, Wang X, Chen W, Mao L, Zhang W, Shi Y, Xie J, Yang R. Epidermal stem cell-derived exosomes improve wound healing by promoting the proliferation and migration of human skin fibroblasts. BURNS & TRAUMA 2024; 12:tkae047. [PMID: 39687464 PMCID: PMC11647520 DOI: 10.1093/burnst/tkae047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 07/16/2024] [Accepted: 08/01/2024] [Indexed: 12/18/2024]
Abstract
Background Epidermal stem cells (ESCs) are primarily located in the basal layer of the epidermis and play a crucial role in wound healing. ESCs-derived exosomes (ESCs-Exo) are emerging as promising candidates for skin regeneration and wound healing. However, the underlying mechanisms remain unclear. This study aims to investigate the role and mechanisms of ESCs-Exo in promoting the proliferation, migration, and collagen synthesis of human skin fibroblasts (HSFBs). Methods This study generated, isolated, and characterized ESC-Exos. The effects of ESCs-Exo on the proliferation of human skin fibroblasts (HSFBs) were detected via Cell Counting Kit-8 (CCK8), 5-Ethynyl-2'-deoxyuridine (EdU), and Proliferating Cell Nuclear Antigen (PCNA) and Marker of Proliferation Ki-67 (MKI67) gene expression methods. The effect of ESCs-Exo on the migration of HSFBs was detected via a transwell assay and a scratch test. The concentrations of collagen secreted by the HSFBs and the mRNAs of the two kinds of collagen expressed by the HSFBs were analyzed. We also analyzed the phosphorylation of Protein Kinase N1 (PKN1) and the expression of cyclins via western blotting. Finally, the effect of ESCs-Exo on wound healing was verified by animal experiments, and the key genes and signaling pathways of ESCs-Exo were excavated by transcriptomic analysis. Results Western blotting revealed that the exosomes of ESCs highly expressed established markers such as Alix, CD63, and CD9. ESC-Exos significantly promoted HSFB proliferation and migration in a dose-dependent manner, as well as HSFB collagen synthesis, and effectively increased the ratio of collagen III/I. In addition, bioinformatics analysis showed that the expression of key gene C-X-C motif chemokine ligand 9 was lower in the ESCs-Exo group, which may promote wound healing by regulating PKN1-cyclin and tumor necrosis factor signaling pathways. Animal experiments demonstrated that ESCs-Exo could reduce inflammation and accelerate wound healing. Conclusions In this study, we found that ESCs-Exo may improve wound healing by promoting the proliferation and migration of HSFBs.
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Affiliation(s)
- Deni Kang
- Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Yuexiu District, Guangzhou City, Guangdong Province, 510180, China
| | - Xiaoxiang Wang
- Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Yuexiu District, Guangzhou City, Guangdong Province, 510062, China
| | - Wentao Chen
- Department of Medical cosmetology, Foshan Second People's Hospital, 78 Weiguo Road, Chancheng District, Foshan City, Guangdong Province, 528000, China
| | - Lujia Mao
- Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, South China University of Technology, 1 Panfu Road, Yuexiu District, Guangzhou City, Guangdong Province, 510180, China
| | - Weiqiang Zhang
- The First Clinical Medical College, Guangdong Medical University, 2 Wenming East Road, Xiashan District, Zhanjiang City, Guangdong Province, 524002, China
| | - Yan Shi
- Department of Plastic, Medical Center of Burn Plastic and Wound Repair, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwai Zheng Street, Donghu District, Nanchang City, Jiangxi Province, 330006, China
| | - Julin Xie
- Department of Burns, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan Second Road, Yuexiu District, Guangzhou City, Guangdong Province, 510062, China
| | - Ronghua Yang
- Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, Guangzhou Medical University, 1 Panfu Road, Yuexiu District, Guangzhou City, Guangdong Province, 510180, China
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10
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Chiang BJ, Mao SH, Chen TS, Chung SD, Chien CT. Adipose stem-cell-derived microvesicles ameliorate long-term bladder ischemia-induced bladder underactivity. J Formos Med Assoc 2024:S0929-6646(24)00565-5. [PMID: 39658414 DOI: 10.1016/j.jfma.2024.12.006] [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: 10/04/2024] [Revised: 11/01/2024] [Accepted: 12/03/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND/PURPOSE The mechanism for long-term hypoxia/ischemia induced bladder underactivity is uncertain. It requires an effectively therapeutic treatment. Therefore, we determined the pathophysiologic mechanisms of long-term bilateral partial iliac arterial occlusion (BPAO)-induced bladder underactivity and explored the therapeutic potential of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs) on BPAO-induced bladder dysfunction. METHODS The study included four groups: sham, BPAO, BPAO + ADSCs, and BPAO + ADSC-MVs. ADSCs or ADSC-MVs were isolated, characterized with specific CD markers and injected through the femoral artery to the rat bladders. Real-time laser speckle contrast imaging evaluated bladder microcirculation after BPAO. The transcystometrogram, pelvic nerve activity, bladder histology, immunohistochemistry, and lipid peroxidation assays were conducted after 4-week BPAO induction. The molecular mechanisms of bladder expression of purinergic P2X2/P2X3 and cholinergic M2/M3 receptors for regulating bladder contractility, nerve growth factor (NGF) for nerve injury repair, and collagen-1 for fibrosis were evaluated. RESULTS Long-term BPAO significantly reduced bladder microcirculation, prolonged the intercontraction interval, decreased voiding volume, increased residual urine volume, lengthened phase 1 contraction, shortened phase 2 contraction, increased leukocytes and CD68 infiltration, increased malondialdehyde levels, and decreased levels of P2X3 and M3 receptors. ADSC-MVs were more efficient than ADSCs in improving BPAO induced parameters, recovering P2X3 and M3 receptors, increasing NGF expression, and decreasing collagen-1 expression in the bladder. CONCLUSIONS ADSC-derived MVs were better than ADSCs to improve long-term BPAO-induced detrusor underactivity, bladder ischemia, and oxidative stress. ADSC-MVs through the therapeutic action of ameliorating inflammation, improving purinergic/cholinergic signaling and neuronal regeneration, and decreasing fibrosis improved BPAO-induced bladder underactivity.
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Affiliation(s)
- Bing-Juin Chiang
- College of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 24205, Taiwan; Department of Urology, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City, 23148, Taiwan; Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan
| | - Su-Han Mao
- College of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City, 24205, Taiwan; Department of Urology, Cardinal Tien Hospital, No.362, Zhongzheng Rd., Xindian Dist., New Taipei City, 23148, Taiwan; Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan
| | - Tung-Sheng Chen
- Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan.
| | - Shiu-Dong Chung
- Division of Urology, Department of Surgery, Far-Eastern Memorial Hospital, No. 21, Section 2, Nanya S. Road, Banqiao Dist., New Taipei City, 220, Taiwan; Department of Nursing, College of Healthcare & Management, Asia Eastern University of Science and Technology, No.58, Sec.2, Sihchuan Rd., Banciao District, New Taipei City, 220303, Taiwan; General Education Center, Asia Eastern University of Science and Technology, No.58, Sec.2, Sihchuan Rd., Banciao District, New Taipei City, 220303, Taiwan.
| | - Chiang-Ting Chien
- Department of Life Science, College of Science, National Taiwan Normal University, 162, Section 1, Heping E. Rd., Taipei, 106, Taiwan.
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11
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Sarvari M, Alavi-Moghadam S, Aghayan HR, Tayanloo-Beik A, Payab M, Tootee A, Sajjadi-Jazi SM, Larijani B, Arjmand B. Stem cells researches and therapies towards endocrine diseases treatment; strategies, challenges, and opportunities. J Diabetes Metab Disord 2024; 23:1461-1467. [PMID: 39610510 PMCID: PMC11599503 DOI: 10.1007/s40200-020-00674-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Accepted: 10/27/2020] [Indexed: 02/06/2023]
Abstract
Due to the limitations of organ transplantation and the urgent need for treatment of chronic diseases, the benefit of stem cells for treatment has been studied and evaluated as an effective approach worldwide. One of the leading countries in this field is Iran. In this respect, several research and treatment institutes, including endocrinology and metabolism research institute are active in the use of stem cells in Iran. Herein, the aim is to review strategies, challenges, and opportunities for stem cell research and treatment in endocrinology and metabolism research institute.
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Affiliation(s)
- Masoumeh Sarvari
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Aghayan
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Tootee
- Diabetes Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Sayed Mahmoud Sajjadi-Jazi
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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12
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Das P, Pal D, Roy S, Chaudhuri S, Kesh SS, Basak P, Nandi SK. Unveiling advanced strategies for therapeutic stem cell interventions in severe burn injuries: a comprehensive review. Int J Surg 2024; 110:6382-6401. [PMID: 38869979 PMCID: PMC11487052 DOI: 10.1097/js9.0000000000001812] [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: 02/03/2024] [Accepted: 05/29/2024] [Indexed: 06/15/2024]
Abstract
This comprehensive review explores the complex terrain of stem cell therapies as a potential therapeutic frontier in the healing of complicated burn wounds. Serious tissue damage, impaired healing processes, and possible long-term consequences make burn wounds a complex problem. An in-depth review is required since, despite medical progress, existing methods for treating severe burn wounds have significant limitations. Burn wounds are difficult to heal because they cause extensive tissue damage. The challenges of burn injury-induced tissue regeneration and functional recovery are also the subject of this review. Although there is a lot of promise in current stem cell treatments, there are also some limitations with scalability, finding the best way to transport the cells, and finding consistent results across different types of patients. To shed light on how to improve stem cell interventions to heal severe burn wounds, this review covers various stem cell applications in burn wounds and examines these obstacles. To overcome these obstacles, one solution is to enhance methods of stem cell distribution, modify therapies according to the severity of the burn, and conduct more studies on how stem cell therapy affects individual patients. Novel solutions may also be possible through the combination of cutting-edge technologies like nanotechnology and biotechnology. This review seeks to increase stem cell interventions by analyzing present challenges and suggesting strategic improvements. The goal is to provide a more effective and tailored way to repair serious burn wounds.
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Affiliation(s)
- Pratik Das
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
- School of Bioscience and Engineering, Jadavpur University
| | - Debajyoti Pal
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Sudipta Roy
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
| | - Shubhamitra Chaudhuri
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Shyam S. Kesh
- Department of Veterinary Clinical Complex, West Bengal University of Animal and Fishery Sciences, Kolkata, India
| | - Piyali Basak
- School of Bioscience and Engineering, Jadavpur University
| | - Samit K. Nandi
- Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences
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13
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González-Gil A, Sánchez-Maldonado B, Rojo C, Flor-García M, Queiroga FL, Ovalle S, Ramos-Ruiz R, Fuertes-Recuero M, Picazo RA. Proneurogenic actions of follicle-stimulating hormone on neurospheres derived from ovarian cortical cells in vitro. BMC Vet Res 2024; 20:372. [PMID: 39160565 PMCID: PMC11334536 DOI: 10.1186/s12917-024-04203-8] [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: 01/26/2024] [Accepted: 07/23/2024] [Indexed: 08/21/2024] Open
Abstract
BACKGROUND Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. RESULTS In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. CONCLUSIONS FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.
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Affiliation(s)
- Alfredo González-Gil
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Avda. Puerta de Hierro SN, Madrid, 28040, Spain.
| | - Belén Sánchez-Maldonado
- Department of Animal Medicine and Surgery, School of Veterinary Medicine, Complutense University of Madrid, Madrid, 28040, Spain
| | - Concepción Rojo
- Department of Anatomy and Embriology, School of Veterinary Medicine, University Complutense of Madrid, Madrid, 28040, Spain
| | - Miguel Flor-García
- Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CBMSO), Spanish Research Council (CSIC)-Universidad Autónoma de Madrid, Madrid, 28049, Spain
- Department of Molecular Biology, Faculty of Sciences, Universidad Autónoma de Madrid, Madrid, 28049, Spain
| | - Felisbina Luisa Queiroga
- Centre for the Study of Animal Science, CECA-ICETA, University of Porto, Porto, Portugal.
- Animal and Veterinary Research Centre (CECAV), University of Trás-os-Montes and Alto Douro, Quinta dos Prados, Vila Real, 5000-801, Portugal.
| | - Susana Ovalle
- Genomic Unit Cantoblanco, Fundación Parque Científico de Madrid. C/ Faraday 7, Madrid, 28049, Spain
| | - Ricardo Ramos-Ruiz
- Genomic Unit Cantoblanco, Fundación Parque Científico de Madrid. C/ Faraday 7, Madrid, 28049, Spain
| | - Manuel Fuertes-Recuero
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Avda. Puerta de Hierro SN, Madrid, 28040, Spain
| | - Rosa Ana Picazo
- Department of Physiology, School of Veterinary Medicine, Complutense University of Madrid, Avda. Puerta de Hierro SN, Madrid, 28040, Spain
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14
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Garroni G, Cruciani S, Serra D, Pala R, Coradduzza D, Cossu ML, Ginesu GC, Ventura C, Maioli M. Effects of the MCF-7 Exhausted Medium on hADSC Behaviour. Int J Mol Sci 2024; 25:7026. [PMID: 39000134 PMCID: PMC11241546 DOI: 10.3390/ijms25137026] [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: 05/31/2024] [Revised: 06/19/2024] [Accepted: 06/24/2024] [Indexed: 07/16/2024] Open
Abstract
Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype.
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Affiliation(s)
- Giuseppe Garroni
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
| | - Sara Cruciani
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
| | - Diletta Serra
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
| | - Renzo Pala
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
| | - Donatella Coradduzza
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
| | - Maria Laura Cossu
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy; (M.L.C.); (G.C.G.)
| | - Giorgio Carlo Ginesu
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, Viale San Pietro 8, 07100 Sassari, Italy; (M.L.C.); (G.C.G.)
| | - Carlo Ventura
- National Laboratory of Molecular Biology and Stem Cell Bioengineering of the National Institute of Biostructures and Biosystems (NIBB) c/o Eldor Lab, Via Corticella 183, 40129 Bologna, Italy;
| | - Margherita Maioli
- Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy; (G.G.); (S.C.); (D.S.); (R.P.); (D.C.)
- Center for Developmental Biology and Reprogramming (CEDEBIOR), Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
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15
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Taherian M, Bayati P, Mojtabavi N. Stem cell-based therapy for fibrotic diseases: mechanisms and pathways. Stem Cell Res Ther 2024; 15:170. [PMID: 38886859 PMCID: PMC11184790 DOI: 10.1186/s13287-024-03782-5] [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] [Received: 01/29/2024] [Accepted: 06/04/2024] [Indexed: 06/20/2024] Open
Abstract
Fibrosis is a pathological process, that could result in permanent scarring and impairment of the physiological function of the affected organ; this condition which is categorized under the term organ failure could affect various organs in different situations. The involvement of the major organs, such as the lungs, liver, kidney, heart, and skin, is associated with a high rate of morbidity and mortality across the world. Fibrotic disorders encompass a broad range of complications and could be traced to various illnesses and impairments; these could range from simple skin scars with beauty issues to severe rheumatologic or inflammatory disorders such as systemic sclerosis as well as idiopathic pulmonary fibrosis. Besides, the overactivation of immune responses during any inflammatory condition causing tissue damage could contribute to the pathogenic fibrotic events accompanying the healing response; for instance, the inflammation resulting from tissue engraftment could cause the formation of fibrotic scars in the grafted tissue, even in cases where the immune system deals with hard to clear infections, fibrotic scars could follow and cause severe adverse effects. A good example of such a complication is post-Covid19 lung fibrosis which could impair the life of the affected individuals with extensive lung involvement. However, effective therapies that halt or slow down the progression of fibrosis are missing in the current clinical settings. Considering the immunomodulatory and regenerative potential of distinct stem cell types, their application as an anti-fibrotic agent, capable of attenuating tissue fibrosis has been investigated by many researchers. Although the majority of the studies addressing the anti-fibrotic effects of stem cells indicated their potent capabilities, the underlying mechanisms, and pathways by which these cells could impact fibrotic processes remain poorly understood. Here, we first, review the properties of various stem cell types utilized so far as anti-fibrotic treatments and discuss the challenges and limitations associated with their applications in clinical settings; then, we will summarize the general and organ-specific mechanisms and pathways contributing to tissue fibrosis; finally, we will describe the mechanisms and pathways considered to be employed by distinct stem cell types for exerting anti-fibrotic events.
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Affiliation(s)
- Marjan Taherian
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Paria Bayati
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Nazanin Mojtabavi
- Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
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16
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Liu W, Zhang C, Jiang F, Tan Y, Qin B. From theory to therapy: a bibliometric and visual study of stem cell advancements in age-related macular degeneration. Cytotherapy 2024; 26:616-631. [PMID: 38483361 DOI: 10.1016/j.jcyt.2024.02.022] [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: 12/07/2023] [Revised: 02/26/2024] [Accepted: 02/26/2024] [Indexed: 05/26/2024]
Abstract
BACKGROUND AIMS Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, offer groundbreaking therapeutic potential for degenerative diseases and cellular repair. Despite their significance, a comprehensive bibliometric analysis in this field, particularly in relation to age-related macular degeneration (AMD), is yet to be conducted. This study aims to map the foundational and emerging areas in stem cell and AMD research through bibliometric analysis. METHODS This study analyzed articles and reviews on stem cells and AMD from 2000 to 2022, sourced from the Web of Science Core Collection. We used VOSviewer and CiteSpace for analysis and visualization of data pertaining to countries, institutions, authors, journals, references and key words. Statistical analyses were conducted using R language and Microsoft Excel 365. RESULTS In total, 539 publications were included, indicating an increase in global literature on stem cells and AMD from 2000 to 2022. The USA was the leading contributor, with 239 papers and the highest H-index, also the USA had the highest average citation rate per article (59.82). Notably, 50% of the top 10 institutions were from the USA, with the University of California system being the most productive. Key authors included Masayo Takahashi, Michiko Mandai, Dennis Clegg, Pete J. Coffey, Boris Stanzel, and Budd A. Tucker. Investigative Ophthalmology & Visual Science published the majority of relevant papers (n = 27). Key words like "clinical trial," "stem cell therapy," "retinal organoid," and "retinal progenitor cells" were predominant. CONCLUSIONS Research on stem cells and AMD has grown significantly, highlighting the need for increased global cooperation. Current research prioritizes the relationship between "ipsc," "induced pluripotent stem cell," "cell culture," and "human embryonic stem cell." As stem cell culture and safety have advanced, focus has shifted to prognosis and complications post-transplantation, signifying the movement of stem cell research from labs to clinical settings.
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Affiliation(s)
| | | | | | - Yao Tan
- Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha, China; Postdoctoral Station of Clinical Medicine, The Third Xiangya Hospital, Central South University, Changsha City, China.
| | - Bo Qin
- Shenzhen Aier Eye Hospital, Aier Eye Hospital, Jinan University, Shenzhen, China.
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17
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Gbelcová H, Rimpelová S, Jariabková A, Macášek P, Priščáková P, Ruml T, Šáchová J, Kubovčiak J, Kolář M, Vítek L. Highly variable biological effects of statins on cancer, non-cancer, and stem cells in vitro. Sci Rep 2024; 14:11830. [PMID: 38782983 PMCID: PMC11116523 DOI: 10.1038/s41598-024-62615-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: 02/21/2024] [Accepted: 05/20/2024] [Indexed: 05/25/2024] Open
Abstract
Statins, the drugs used for the treatment of hypercholesterolemia, have come into the spotlight not only as chemoadjuvants, but also as potential stem cell modulators in the context of regenerative therapy. In our study, we compared the in vitro effects of all clinically used statins on the viability of human pancreatic cancer (MiaPaCa-2) cells, non-cancerous human embryonic kidney (HEK 293) cells and adipose-derived mesenchymal stem cells (ADMSC). Additionally, the effect of statins on viability of MiaPaCa-2 and ADMSC cells spheroids was tested. Furthermore, we performed a microarray analysis on ADMSCs treated with individual statins (12 μM) and compared the importance of the effects of statins on gene expression between stem cells and pancreatic cancer cells. Concentrations of statins that significantly affected cancer cells viability (< 40 μM) did not affect stem cells viability after 24 h. Moreover, statins that didn´t affect viability of cancer cells grown in a monolayer, induce the disintegration of cancer cell spheroids. The effect of statins on gene expression was significantly less pronounced in stem cells compared to pancreatic cancer cells. In conclusion, the low efficacy of statins on non-tumor and stem cells at concentrations sufficient for cancer cells growth inhibition, support their applicability in chemoadjuvant tumor therapy.
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Affiliation(s)
- Helena Gbelcová
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, 813 72, Slovak Republic.
| | - Silvie Rimpelová
- Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, 166 28, Czech Republic
| | - Adriana Jariabková
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, 813 72, Slovak Republic
| | - Patrik Macášek
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, 813 72, Slovak Republic
| | - Petra Priščáková
- Institute of Medical Biology, Genetics and Clinical Genetics, Faculty of Medicine, Comenius University, Bratislava, 813 72, Slovak Republic
| | - Tomáš Ruml
- Department of Biochemistry and Microbiology, University of Chemistry and Technology, Prague, 166 28, Czech Republic
| | - Jana Šáchová
- Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, 142 20, Czech Republic
| | - Jan Kubovčiak
- Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, 142 20, Czech Republic
| | - Michal Kolář
- Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics, Czech Academy of Sciences, Prague, 142 20, Czech Republic
- Department of Informatics and Chemistry, University of Chemistry and Technology, Prague, 166 28, Czech Republic
| | - Libor Vítek
- Institute of Medical Biochemistry and Laboratory Diagnostics, and 4Th Department of Internal Medicine, 1St Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, 121 08, Czech Republic
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18
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Vu TD, Luong DT, Ho TT, Nguyen Thi TM, Singh V, Chu DT. Drug repurposing for regenerative medicine and cosmetics: Scientific, technological and economic issues. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2024; 207:337-353. [PMID: 38942543 DOI: 10.1016/bs.pmbts.2024.02.005] [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: 06/30/2024]
Abstract
Regenerative medicine and cosmetics are currently two outstanding fields for drug discovery. Although many pharmaceutical products for regenerative medicine and cosmetics have received approval by official agencies, several challenges are still needed to overcome, especially financial and time issues. As a result, drug repositioning, which is the usage of previously approved drugs for new treatment, stands out as a promising approach to tackle these problems. Recently, increasing scientific evidence is collected to demonstrate the applicability of this novel method in the field of regenerative medicine and cosmetics. Experts in drug development have also taken advantage of novel technologies to discover new candidates for repositioning purposes following computational approach, one of two main approaches of drug repositioning. Therefore, numerous repurposed candidates have obtained approval to enter the market and have witnessed financial success such as minoxidil and fingolimod. The benefits of drug repositioning are undeniable for regenerative medicine and cosmetics. However, some aspects still need to be carefully considered regarding this method including actual effectiveness during clinical trials, patent regulations, data integration and analysis, publicly unavailable databases as well as environmental concerns and more effort are required to overcome these obstacles.
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Affiliation(s)
- Thuy-Duong Vu
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam
| | - Duc Tri Luong
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam
| | - Thuy-Tien Ho
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam
| | - Thuy-My Nguyen Thi
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam
| | - Vijai Singh
- Department of Biosciences, School of Science, Indrashil University, Rajpur, Mehsana, India
| | - Dinh-Toi Chu
- Center for Biomedicine and Community Health, International School, Vietnam National University, Hanoi, Vietnam; Faculty of Applied Sciences, International School, Vietnam National University, Hanoi, Vietnam.
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19
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Rajput SN, Naeem BK, Ali A, Salim A, Khan I. Expansion of human umbilical cord derived mesenchymal stem cells in regenerative medicine. World J Stem Cells 2024; 16:410-433. [PMID: 38690517 PMCID: PMC11056638 DOI: 10.4252/wjsc.v16.i4.410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/01/2024] [Accepted: 03/18/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND Stem cells are undifferentiated cells that possess the potential for self-renewal with the capacity to differentiate into multiple lineages. In humans, their limited numbers pose a challenge in fulfilling the necessary demands for the regeneration and repair of damaged tissues or organs. Studies suggested that mesenchymal stem cells (MSCs), necessary for repair and regeneration via transplantation, require doses ranging from 10 to 400 million cells. Furthermore, the limited expansion of MSCs restricts their therapeutic application. AIM To optimize a novel protocol to achieve qualitative and quantitative expansion of MSCs to reach the targeted number of cells for cellular transplantation and minimize the limitations in stem cell therapy protocols. METHODS Human umbilical cord (hUC) tissue derived MSCs were obtained and re-cultured. These cultured cells were subjected to the following evaluation procedures: Immunophenotyping, immunocytochemical staining, trilineage differentiation, population doubling time and number, gene expression markers for proliferation, cell cycle progression, senescence-associated β-galactosidase assay, human telomerase reverse transcriptase (hTERT) expression, mycoplasma, cytomegalovirus and endotoxin detection. RESULTS Analysis of pluripotent gene markers Oct4, Sox2, and Nanog in recultured hUC-MSC revealed no significant differences. The immunophenotypic markers CD90, CD73, CD105, CD44, vimentin, CD29, Stro-1, and Lin28 were positively expressed by these recultured expanded MSCs, and were found negative for CD34, CD11b, CD19, CD45, and HLA-DR. The recultured hUC-MSC population continued to expand through passage 15. Proliferative gene expression of Pax6, BMP2, and TGFb1 showed no significant variation between recultured hUC-MSC groups. Nevertheless, a significant increase (P < 0.001) in the mitotic phase of the cell cycle was observed in recultured hUC-MSCs. Cellular senescence markers (hTERT expression and β-galactosidase activity) did not show any negative effect on recultured hUC-MSCs. Additionally, quality control assessments consistently confirmed the absence of mycoplasma, cytomegalovirus, and endotoxin contamination. CONCLUSION This study proposes the development of a novel protocol for efficiently expanding stem cell population. This would address the growing demand for larger stem cell doses needed for cellular transplantation and will significantly improve the feasibility of stem cell based therapies.
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Affiliation(s)
- Shafiqa Naeem Rajput
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Bushra Kiran Naeem
- Surgical Unit 4, Dr. Ruth KM Pfau Civil Hospital, Karachi 74400, Pakistan
| | - Anwar Ali
- Department of Physiology, University of Karachi, Karachi 75270, Pakistan
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
- Center for Regenerative Medicine and Stem Cells Research, and Department of Ophthalmology and Visual Sciences, The Aga Khan University, Karachi 74800, Sindh, Pakistan.
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20
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Bydon M, Qu W, Moinuddin FM, Hunt CL, Garlanger KL, Reeves RK, Windebank AJ, Zhao KD, Jarrah R, Trammell BC, El Sammak S, Michalopoulos GD, Katsos K, Graepel SP, Seidel-Miller KL, Beck LA, Laughlin RS, Dietz AB. Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury: Phase I trial. Nat Commun 2024; 15:2201. [PMID: 38561341 PMCID: PMC10984970 DOI: 10.1038/s41467-024-46259-y] [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: 05/11/2023] [Accepted: 02/21/2024] [Indexed: 04/04/2024] Open
Abstract
Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.
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Affiliation(s)
- Mohamad Bydon
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA.
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA.
| | - Wenchun Qu
- Physical Medicine and Rehabilitation, Mayo Clinic, Jacksonville, FL, USA
| | - F M Moinuddin
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | - Ronald K Reeves
- Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA
| | | | - Kristin D Zhao
- Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA
| | - Ryan Jarrah
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | - Brandon C Trammell
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | - Sally El Sammak
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | - Giorgos D Michalopoulos
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | - Konstantinos Katsos
- Neuro-Informatics Laboratory, Mayo Clinic, Rochester, MN, USA
- Department of Neurological Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | - Lisa A Beck
- Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA
| | | | - Allan B Dietz
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
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21
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Fan J, Xie J, Liao Y, Lai B, Zhou G, Lian W, Xiong J. Human umbilical cord-derived mesenchymal stem cells and auto-crosslinked hyaluronic acid gel complex for treatment of intrauterine adhesion. Aging (Albany NY) 2024; 16:6273-6289. [PMID: 38568100 PMCID: PMC11042966 DOI: 10.18632/aging.205704] [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: 10/24/2023] [Accepted: 03/09/2024] [Indexed: 04/23/2024]
Abstract
OBJECTIVE The purpose of this study was to explore the therapeutic characteristics of mesenchymal stem cells generated from human umbilical cord (hUC-MSCs) when utilized in conjunction with auto-crosslinked hyaluronic acid gel (HA-gel) for the management of intrauterine adhesion (IUA). The goal was to see how this novel therapy could enhance healing and improve outcomes for IUA patients. METHODS In this study, models of intrauterine adhesion (IUA) were established in Sprague-Dawley (SD) rats, which were then organized and divided into hUC-MSCs groups. The groups involved: hUC-MSCs/HA-gel group, control group, and HA-gel group. Following treatment, the researchers examined the uterine cavities and performed detailed analyses of the endometrial tissues to determine the effectiveness of the interventions. RESULTS The results indicated that in comparison with to the control group, both HA-gel, hUC-MSCs, and hUC-MSCs/HA-gel groups showed partial repair of IUA. However, in a more notable fashion transplantation of hUC-MSCs/HA-gel complex demonstrated significant dual repair effects. Significant outcomes were observed in the group treated with hUC-MSCs and HA-gel, they showed thicker endometrial layers, less fibrotic tissue, and a higher number of endometrial glands. This treatment strategy also resulted in a significant improvement in fertility restoration, indicating a profound therapeutic effect. CONCLUSIONS The findings of this study suggest that both HA-gel, hUC-MSCs, and hUC-MSCs/HA-gel complexes have the potential for partial repair of IUA and fertility restoration caused by endometrium mechanical injury. Nonetheless, the transplantation of the hUC-MSCs/HA-gel complex displayed exceptional dual healing effects, combining effective anti-adhesive properties with endometrial regeneration stimuli.
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Affiliation(s)
- Jiaying Fan
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Jingying Xie
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Yunsheng Liao
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Baoyu Lai
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Guixin Zhou
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Wenqin Lian
- Department of Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
| | - Jian Xiong
- Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
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22
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Li Y, Zhao L, Li S, Ruan D, Xiong L, Tang J, Hu M, Wang Y, Huang W, Li L, Zhao Z. Skin-derived precursor conditioned medium alleviated photoaging via early activation of TGF-β/Smad signaling pathway by thrombospondin1: In vitro and in vivo studies. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY. B, BIOLOGY 2024; 253:112873. [PMID: 38412778 DOI: 10.1016/j.jphotobiol.2024.112873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Revised: 02/19/2024] [Accepted: 02/20/2024] [Indexed: 02/29/2024]
Abstract
Photoaging is one major exogenous factor of skin aging. Efficacy and safety of current anti-photoaging therapies remained to be improved. Our previous studies indicated that skin-derived precursors (SKPs) alleviated photodamage by early activation of TGF-β/Smad signaling pathway via thrombospondin1 (TSP1). However, the research concerning SKP conditioned medium (SKP-CM) has never been reported. In the current study, we aimed to explore the anti-photoaging effects of SKP-CM both in vitro and in vivo, and to elucidate the possible mechanisms. Mouse SKP-CM (mSKP-CM) collection was optimized by a comparative method. The concentration of protein and growth factors in mSKP-CM was detected using BCA protein assay kit and growth factor protein chip. The anti-photoaging effects of mSKP-CM and its regulation of key factors in the TGF-β/Smad signaling pathway were explored using UVA + UVB photoaged mouse fibroblasts (mFBs) and nude mice dorsal skin. The research revealed that mSKP-CM contained significantly higher-concentration of protein and growth factors than mouse mesenchymal stem cell conditioned medium (mDMSC-CM). mSKP-CM alleviated mFBs photoaging by restoring cell viability and relieving senescence and death. ELISA, qRT-PCR, and western blot results implied the potential mechanisms were associated with the early activation of TGF-β/Smad signaling pathway by TSP1. In vivo experiments demonstrated that compared with the topical intradermal mDMSC-CM injection and retinoic acid cream application, the photodamaged mice dorsal skin intradermally injected with mSKP-CM showed significantly better improvement. Consistent with the in vitro results, both western blot and immunohistochemistry results confirmed that protein expression of TSP1, smad2/3, p-smad2/3, TGF-β1, and collagen I increased, and matrix metalloproteinases decreased. In summary, both in vitro and in vivo experiments demonstrated that mSKP-CM alleviated photoaging through an early activation of TGF-β/Smad signaling pathway via TSP1. SKP-CM may serve as a novel and promising cell-free therapeutical approach for anti-photoaging treatment and regenerative medicine.
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Affiliation(s)
- Yiming Li
- Department of Dermatology, Sichuan Second Hospital of TCM, Chengdu, Sichuan 610041, China; Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
| | - Lingyun Zhao
- Department of Dermatology and Venerology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Shiyi Li
- Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Danhua Ruan
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Lidan Xiong
- Center of Cosmetics Evaluation, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Jie Tang
- Center of Cosmetics Evaluation, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Meng Hu
- State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Yixin Wang
- Department of Dermatology and Venerology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Wen Huang
- Laboratory of Ethnopharmacology, Tissue-orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Li Li
- Department of Dermatology and Venerology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China; Center of Cosmetics Evaluation, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhiwei Zhao
- Department of Anatomy, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, China
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23
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Mohammadi M, Mansouri K, Mohammadi P, Pournazari M, Najafi H. Exosomes in renal cell carcinoma: challenges and opportunities. Mol Biol Rep 2024; 51:443. [PMID: 38520545 DOI: 10.1007/s11033-024-09384-x] [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: 01/14/2024] [Accepted: 02/26/2024] [Indexed: 03/25/2024]
Abstract
Renal cell carcinoma (RCC) is the most common type of kidney cancer that accounts for approximately 2-3% of adult malignancies. Among the primary treatment methods for this type of cancer are surgery and targeted treatment. Still, due to less than optimal effectiveness, there are problems such as advanced distant metastasis, delayed diagnosis, and drug resistance that continue to plague patients. In recent years, therapeutic advances have increased life expectancy and effective treatment in renal cell carcinoma patients. One of these methods is the use of stem cells. Although the therapeutic effects of stem cells, especially mesenchymal stem cells, are still impressive, today, extracellular vesicles (EVs) as carrying molecules and various mediators in intercellular communications, having a central role in tumorigenesis, metastasis, immune evasion, and drug response, and on the other hand, due to its low immunogenicity and strong regulatory properties of the immune system, has received much attention from researchers and doctors. Despite the increasing interest in exosomes as the most versatile type of EVs, the heterogeneity of their efficacy presents challenges and, on the other hand, exciting opportunities for diagnostic and clinical interventions.In the upcoming article, we will review the various aspects of exosomes' effects in the prevention, treatment, and progress of renal cell carcinoma and also ways to optimize them to strengthen their positive sides.
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Affiliation(s)
- Mahan Mohammadi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Kamran Mansouri
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Pantea Mohammadi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehran Pournazari
- Clinical Research Development Center, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Houshang Najafi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
- Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
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24
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Kesavan R, Sheela Sasikumar C, Narayanamurthy VB, Rajagopalan A, Kim J. Management of Diabetic Foot Ulcer with MA-ECM (Minimally Manipulated Autologous Extracellular Matrix) Using 3D Bioprinting Technology - An Innovative Approach. INT J LOW EXTR WOUND 2024; 23:161-168. [PMID: 34636693 DOI: 10.1177/15347346211045625] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Chronic foot ulcers are the leading cause of prolonged hospitalization and loss of social participation in people with diabetes. Conventional management of diabetic foot ulcers (DFU) is associated with slow healing, high cost, and recurrent visits to the hospital. Currently, the application of autologous lipotransfer is more popular, as the regenerative and reparative effects of fat are well established. Herein we report the efficacy of minimally manipulated extracellular matrix (MA-ECM) prepared from autologous homologous adipose tissue by using 3D bioprinting in DFU (test group) in comparison to the standard wound care (control group). A total of 40 subjects were screened and randomly divided into test and control groups. In the test group, the customized MA-ECM was printed as a scaffold from the patient autologous fat using a 3D bioprinter device and applied to the wound directly. The control group received standard wound care and weekly follow-up was done for all the patients. We evaluated the efficacy of this novel technology by assessing the reduction in wound size and attainment of epithelialization. The patients in the test group (n = 17) showed complete wound closure with re-epithelialization approximately within a period of 4 weeks. On the other hand, most of the patients in the control group (n = 16) who received standard wound dressings care showed a delay in wound healing in comparison to the test group. This technique can be employed as a personalized therapeutic method to accelerate diabetic wound healing and may provide a promising potential alternative approach to protect against lower foot amputation a most common complication in diabetes.
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Affiliation(s)
- Rajesh Kesavan
- Department of Podiatric Surgery, NRA Wound Care Pvt Ltd, Hycare Super speciality Hospital, Chennai, Tamilnadu, India
- SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, India
| | - Changam Sheela Sasikumar
- Department of Clinical Research, S.S. Healthcare, NRA Wound Care Pvt Ltd, Hycare Super Speciality, Hospital, Chennai, Tamilnadu, India
- Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical & Technical Sciences, Saveetha University Chennai, Tamilnadu, India
| | - V B Narayanamurthy
- Department of Plastic Surgery, NRA Wound Care Pvt Ltd, Hycare Super Speciality Hospital, Chennai, Tamilnadu, India
| | - Arvind Rajagopalan
- Department of Orthopedic Surgery, NRA Wound Care Pvt Ltd, Hycare Super Speciality Hospital, Chennai, Tamilnadu, India
| | - Jeehee Kim
- R&D Center, ROKIT AMERICA, 3580 Wilshire Blvd., Los Angeles, CA, USA
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25
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Taninokuchi Tomassoni M, Zhou Y, Braccischi L, Modestino F, Fukuda J, Mosconi C. Trans-Arterial Stem Cell Injection (TASI): The Role of Interventional Radiology in Regenerative Medicine. J Clin Med 2024; 13:910. [PMID: 38337604 PMCID: PMC10856532 DOI: 10.3390/jcm13030910] [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: 12/13/2023] [Revised: 01/19/2024] [Accepted: 02/01/2024] [Indexed: 02/12/2024] Open
Abstract
Regenerative medicine is taking a step forward in treating multiple diseases. The possibility of renewing damaged tissues with stem cells has become a topic of interest in recent decades. Still a relatively new research topic, many issues in this discipline are being addressed, from cell culturing to the study of different graft materials, and, moreover, cell delivery. For instance, direct intravenous injection has a big downfall regarding its lack of precision and poorly targeted treatment. Trans-arterial and direct percutaneous infusion to the aimed tissue/organ are both considered ideal for reaching the desired region but require image guidance to be performed safely and precisely. In this context, interventional radiology becomes pivotal for providing different cell delivery possibilities in every case. In this review, we analyze different basic stem cell therapy concepts and the current and future role of interventional radiology with a focus on trans-arterial delivery.
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Affiliation(s)
- Makoto Taninokuchi Tomassoni
- Department of Radiology, IRRCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (L.B.)
| | - Yinghui Zhou
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Kanagawa, Japan (J.F.)
| | - Lorenzo Braccischi
- Department of Radiology, IRRCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (L.B.)
| | - Francesco Modestino
- Department of Radiology, IRRCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (L.B.)
| | - Junji Fukuda
- Faculty of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501, Kanagawa, Japan (J.F.)
| | - Cristina Mosconi
- Department of Radiology, IRRCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy; (L.B.)
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26
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Sun N, Sun Y, Xing Y, Xu L, Chen Z, Qing L, Wu P, Tang J. Knowledge mapping and research trends of stem cell in wound healing: A bibliometric analysis. Int Wound J 2024; 21:e14587. [PMCID: PMC10830390 DOI: 10.1111/iwj.14587] [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: 10/31/2023] [Revised: 12/06/2023] [Accepted: 12/07/2023] [Indexed: 01/12/2025] Open
Abstract
Wound nonhealing is a common and difficult problem in clinic. Stem cells are pluripotent cells, and their undifferentiated and self‐replicating characteristics have attracted much attention in the regenerative medicine‐related researches. New treatment approaches might result from an understanding of the function of stem cells in wound healing. Using bibliometric techniques, this study proposed to analyse the research status, hotspots, and research trends in stem cell and wound healing. By using the Web of Science Core Collection (WoSCC), we conducted an in‐depth review of publications on stem cells in wound healing from 1999 to 2023. We used scientometric analysis methods to examine annual trends, institutions, countries, journals, authors, keywords, co‐occurrence references and their closed relationship, revealing present hotspots and potential future advancements in this field. We analysed 19 728 English studies and discovered a consistent rise in annual publications. The United States and China were the two countries with the most publications. The most three influential institutions in the field were Shanghai Jiao Tong University, Sun Yat‐sen University, and University of Pittsburgh. International Journal of Molecular Sciences and Biomaterials were considered the most influential journals in this field. International Journal of Molecular Sciences had the most publications, and the most quantity of citations and the highest H‐index were found in Biomaterials . The dual‐map overlay revealed that publications in Molecular/Biology/Genetics and Health/Nursing/Medicine co‐cited journals received the majority of the citations for studies from Molecular/Biology/Immunology and Medicine/Medical/Clinical. In terms of publication production and influence, Fu X stood out among the authors, and Pittenger MF took the top spot in co‐citations. According to the keywords from the analysis, future research should concentrate on the mechanisms through which stem cells promote wound healing. We conducted a thorough analysis of the general information, knowledge base and research hotspots in the field of stem cells and wound healing from 1999 to 2023 by using the VOSviewer, CiteSpace, and other bibliometric analysis tools. It not only provided valuable insights for scholars, but also served as a reliable reference that drives further development in the field and stimulates the interest of researchers.
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Affiliation(s)
- Nianzhe Sun
- Department of OrthopedicsXiangya Hospital, Central South UniversityChangshaChina
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
| | - Yu Sun
- Department of OrthopedicsXiangya Hospital, Central South UniversityChangshaChina
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
| | - Yixuan Xing
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
- Department of EmergencyXiangya Hospital, Central South UniversityChangshaChina
| | - Laiyu Xu
- Department of OrthopedicsThe First Affiliated Hospital, College of Medicine, Zhejiang UniversityHangzhouChina
| | - Zijie Chen
- Department of Hand Surgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Liming Qing
- Department of OrthopedicsXiangya Hospital, Central South UniversityChangshaChina
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
| | - Panfeng Wu
- Department of OrthopedicsXiangya Hospital, Central South UniversityChangshaChina
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
| | - Juyu Tang
- Department of OrthopedicsXiangya Hospital, Central South UniversityChangshaChina
- National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South UniversityChangshaChina
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27
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Giorgi Z, Veneruso V, Petillo E, Veglianese P, Perale G, Rossi F. Biomaterials and Cell Therapy Combination in Central Nervous System Treatments. ACS APPLIED BIO MATERIALS 2024; 7:80-98. [PMID: 38158393 PMCID: PMC10792669 DOI: 10.1021/acsabm.3c01058] [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: 11/09/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 01/03/2024]
Abstract
Current pharmacological and surgical therapies for the central nervous system (CNS) show a limited capacity to reduce the damage progression; that together with the intrinsic limited capability of the CNS to regenerate greatly reduces the hopes of recovery. Among all the therapies proposed, the tissue engineering strategies supplemented with therapeutic stem cells remain the most promising. Neural tissue engineering strategies are based on the development of devices presenting optimal physical, chemical, and mechanical properties which, once inserted in the injured site, can support therapeutic cells, limiting the effect of a hostile environment and supporting regenerative processes. Thus, this review focuses on the employment of hydrogel and nanofibrous scaffolds supplemented with stem cells as promising therapeutic tools for the central and peripheral nervous systems in preclinical and clinical applications.
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Affiliation(s)
- Zoe Giorgi
- Department
of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, piazza Leonardo da Vinci 32, 20133, Milan, Italy
| | - Valeria Veneruso
- Istituto
di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
- Faculty
of Biomedical Sciences, University of Southern
Switzerland (USI), Via
Buffi 13, 6900 Lugano, Switzerland
| | - Emilia Petillo
- Department
of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, piazza Leonardo da Vinci 32, 20133, Milan, Italy
- Istituto
di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
| | - Pietro Veglianese
- Istituto
di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156 Milan, Italy
- Faculty
of Biomedical Sciences, University of Southern
Switzerland (USI), Via
Buffi 13, 6900 Lugano, Switzerland
| | - Giuseppe Perale
- Faculty
of Biomedical Sciences, University of Southern
Switzerland (USI), Via
Buffi 13, 6900 Lugano, Switzerland
- Ludwig
Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstrasse 13, 1200 Vienna, Austria
| | - Filippo Rossi
- Department
of Chemistry, Materials and Chemical Engineering “Giulio Natta”, Politecnico di Milano, piazza Leonardo da Vinci 32, 20133, Milan, Italy
- Faculty
of Biomedical Sciences, University of Southern
Switzerland (USI), Via
Buffi 13, 6900 Lugano, Switzerland
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28
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Ding X, Zhang L, Zhou D, Tang X, He X, Rohani S. The effects of propolis-loaded chitosan nanoparticles and menstrual blood stem cells on LPS-induced ovarian inflammation in the murine ovary in vivo: An in vitro and in vivo study. Reprod Toxicol 2024; 123:108514. [PMID: 38000645 DOI: 10.1016/j.reprotox.2023.108514] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2023] [Revised: 11/13/2023] [Accepted: 11/19/2023] [Indexed: 11/26/2023]
Abstract
Mammary glands infection via Gram-negative bacteria may cause infertility or reduced ovarian function. In the current study, a potential treatment for LPS-induced ovarian inflammation was developed. Propolis was loaded into chitosan nanoparticles and co-administered with menstrual blood stem cells (MenSCs) in mice infused with LPS. Various properties of propolis-loaded chitosan nanoparticles were evaluated using scanning electron microscopy, drug release assay, antibacterial assay, and radical scavenging assay. In vitro studies showed biocompatibility, anti-oxidative, and antibacterial properties of the developed propolis nanoformulation. In vivo study showed that mice treated with co-administration of propolis-loaded chitosan nanoparticles and MenSCs significantly increased the total ovarian follicle reserve in mice infused with LPS. Percentage of mature follicles in co-administration method was around 13.89 ± 1.72 %. Gene expression studies showed that the expression levels of inflammation related cytokines including IL6, IL8, IL-1β, and TNF-α were downregulated in this group compared with other groups. However, the expression levels of PTEN, AKT, FOXO3 did not show a significant difference between groups. The developed treatment may potentially considered as an approach for treating ovarian infection with gram-negative bacteria.
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Affiliation(s)
- Xu Ding
- Department of Reproductive Endocrinology, Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an 710100, China
| | - Lili Zhang
- Department of Obstetrics, The People's Hospital of Leling, Dezhou, 253600, China
| | - Dongmei Zhou
- Department of Reproductive Endocrinology, Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an 710100, China
| | - Xueyuan Tang
- Department of Reproductive Endocrinology, Xi'an International Medical Center Hospital Affiliated to Northwest University, Xi'an 710100, China
| | - Xiao He
- Department of Gynecology and Obstetrics, XD Group Hospital, Xi'an 710077, China.
| | - Saeed Rohani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Widodo W, Widyahening IS, Pratama IK, Kuncoro MW. Prospect of Mesenchymal Stem Cells in Enhancing Nerve Regeneration in Brachial Plexus Injury in Animals: A Systematic Review. THE ARCHIVES OF BONE AND JOINT SURGERY 2024; 12:149-158. [PMID: 38577510 PMCID: PMC10989726 DOI: 10.22038/abjs.2024.68053.3224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 09/22/2022] [Accepted: 01/14/2024] [Indexed: 04/06/2024]
Abstract
Objectives Brachial plexus injuries (BPI), although rare, often results in significant morbidity. Stem cell was thought to be one of BPI treatment modalities because of their nerve-forming regeneration potential. Although there is a possibility for the use of mesenchymal stem cells as one of BPI treatment, it is still limited on animal studies. Therefore, this systematic review aimed to analyze the role of mesenchymal stem cells in nerve regeneration in animal models of brachial plexus injury. Method This study is a systematic review with PROSPERO registration number CRD4202128321. Literature searching was conducted using keywords experimental, animal, brachial plexus injury, mesenchymal stem cell implantation, clinical outcomes, electrophysiological outcomes, and histologic outcomes. Searches were performed in the PubMed, Scopus, and ScienceDirect databases. The risk of bias was assessed using SYRCLE's risk of bias tool for animal studies. The data obtained were described and in-depth analysis was performed. Result Four studies were included in this study involving 183 animals from different species those are rats and rabbits. There was an increase in muscle weight and shortened initial onset time of muscle contraction in the group treated with stem cells. Electrophysiological results showed that mesenchymal stem cells exhibited higher (Compound muscle action potential) CMAP amplitude and shorter CMAP latency than control but not better than autograft. Histological outcomes showed an increase in axon density, axon number, and the formation of connections between nerve cells and target muscles. Conclusion Mesenchymal stem cell implantation to animals with brachial plexus injury showed its ability to regenerate nerve cells as evidenced by clinical, electrophysiological, and histopathological results. However, this systematic study involved experimental animals from various species so that the results cannot be uniformed, and conclusion should be drawn cautiously.
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Affiliation(s)
- Wahyu Widodo
- Department of Orthopaedic and Traumatology Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Indah Suci Widyahening
- Department of Community Medicine, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Irfan Kurnia Pratama
- Department of Orthopaedic and Traumatology Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
| | - Mohamad Walid Kuncoro
- Department of Orthopaedic and Traumatology Cipto Mangunkusumo Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
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Harland N, Knoll J, Amend B, Abruzzese T, Abele H, Jakubowski P, Stenzl A, Aicher WK. Xenogenic Application of Human Placenta-Derived Mesenchymal Stromal Cells in a Porcine Large Animal Model. Cell Transplant 2024; 33:9636897241226737. [PMID: 38323325 PMCID: PMC10851762 DOI: 10.1177/09636897241226737] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Revised: 11/30/2023] [Accepted: 01/02/2024] [Indexed: 02/08/2024] Open
Abstract
In animal models, cell therapies for different diseases or injuries have been very successful. Preclinical studies with cells aiming at a stroke, heart attack, and other emergency situations were promising but sometimes failed translation in clinical situations. We, therefore, investigated if human placenta-derived mesenchymal stromal cells can be injected in pigs without provoking rejection to serve as a xenogenic transplantation model to bridge preclinical animal studies to more promising future preclinical studies. Male human placenta-derived mesenchymal stromal cells were isolated, expanded, and characterized by flow cytometry, in vitro differentiation, and quantitative reverse-transcription polymerase chain reaction to prove their nature. Such cells were injected into the sphincter muscle of the urethrae of female pigs under visual control by cystoscopy employing a Williams needle. The animals were observed over 7 days of follow-up. Reactions of the host to the xenogeneic cells were explored by monitoring body temperature, and inflammatory markers including IL-1ß, CRP, and haptoglobin in blood. After sacrifice on day 7, infiltration of inflammatory cells in the tissue targeted was investigated by histology and immunofluorescence. DNA of injected human cells was detected by PCR. Upon injection in vascularized porcine tissue, human placenta-derived mesenchymal stromal cells were tolerated, and systemic inflammatory parameters were not elevated. DNA of injected cells was detected in situ 7 days after injection, and moderate local infiltration of inflammatory cells was observed. The therapeutic potential of human placenta-derived mesenchymal stromal cells can be explored in porcine large animal models of injury or disease. This seems a promising strategy to explore technologies for cell injections in infarcted hearts or small organs and tissues in therapeutically relevant amounts requiring large animal models to yield meaningful outcomes.
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Affiliation(s)
- Niklas Harland
- Department of Urology, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Jasmin Knoll
- Center for Medical Research, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Bastian Amend
- Department of Urology, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Tanja Abruzzese
- Center for Medical Research, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Harald Abele
- Department of Gynecology and Obstetrics, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Peter Jakubowski
- Department of Gynecology and Obstetrics, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Arnulf Stenzl
- Center for Medical Research, University Hospital, Eberhard Karls University, Tuebingen, Germany
| | - Wilhelm K. Aicher
- Department of Urology, University Hospital, Eberhard Karls University, Tuebingen, Germany
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Arjmand B, Alavi-Moghadam S, Faraji Z, Aghajanpoor-Pasha M, Jalaeikhoo H, Rajaeinejad M, Nikandish M, Faridfar A, Rezazadeh-Mafi A, Rezaei-Tavirani M, Irompour A. The Potential Role of Intestinal Stem Cells and Microbiota for the Treatment of Colorectal Cancer. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1470:115-128. [PMID: 38811486 DOI: 10.1007/5584_2024_803] [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: 05/31/2024]
Abstract
Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer.
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Affiliation(s)
- Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Faraji
- Iranian Cancer Control Center (MACSA), Tehran, Iran
| | | | - Hasan Jalaeikhoo
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Mohsen Rajaeinejad
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Mohsen Nikandish
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Ali Faridfar
- AJA Cancer Epidemiology Research and Treatment Center (AJA-CERTC), AJA University of Medical Sciences, Tehran, Iran
| | - Ahmad Rezazadeh-Mafi
- Department of Radiation Oncology, Imam Hossein Hospital, Shaheed Beheshti Medical University, Tehran, Iran
| | | | - Arsalan Irompour
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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Alnasser SM, Alharbi KS, Almutairy AF, Almutairi SM, Alolayan AM. Autologous Stem Cell Transplant in Hodgkin's and Non-Hodgkin's Lymphoma, Multiple Myeloma, and AL Amyloidosis. Cells 2023; 12:2855. [PMID: 38132175 PMCID: PMC10741865 DOI: 10.3390/cells12242855] [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: 11/12/2023] [Revised: 11/30/2023] [Accepted: 12/05/2023] [Indexed: 12/23/2023] Open
Abstract
Human body cells are stem cell (SC) derivatives originating from bone marrow. Their special characteristics include their capacity to support the formation and self-repair of the cells. Cancer cells multiply uncontrollably and invade healthy tissues, making stem cell transplants a viable option for cancer patients undergoing high-dose chemotherapy (HDC). When chemotherapy is used at very high doses to eradicate all cancer cells from aggressive tumors, blood-forming cells and leukocytes are either completely or partially destroyed. Autologous stem cell transplantation (ASCT) is necessary for patients in those circumstances. The patients who undergo autologous transplants receive their own stem cells (SCs). The transplanted stem cells first come into contact with the bone marrow and then undergo engraftment, before differentiating into blood cells. ASCT is one of the most significant and innovative strategies for treating diseases. Here we focus on the treatment of Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma, and AL amyloidosis, using ASCT. This review provides a comprehensive picture of the effectiveness and the safety of ASCT as a therapeutic approach for these diseases, based on the currently available evidence.
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Affiliation(s)
- Sulaiman Mohammed Alnasser
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia; (K.S.A.); (A.F.A.)
| | - Khalid Saad Alharbi
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia; (K.S.A.); (A.F.A.)
| | - Ali F. Almutairy
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Buraydah 51452, Saudi Arabia; (K.S.A.); (A.F.A.)
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Hu X, Wu H, Yong X, Wang Y, Yang S, Fan D, Xiao Y, Che L, Shi K, Li K, Xiong C, Zhu H, Qian Z. Cyclical endometrial repair and regeneration: Molecular mechanisms, diseases, and therapeutic interventions. MedComm (Beijing) 2023; 4:e425. [PMID: 38045828 PMCID: PMC10691302 DOI: 10.1002/mco2.425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 10/21/2023] [Accepted: 10/27/2023] [Indexed: 12/05/2023] Open
Abstract
The endometrium is a unique human tissue with an extraordinary ability to undergo a hormone-regulated cycle encompassing shedding, bleeding, scarless repair, and regeneration throughout the female reproductive cycle. The cyclical repair and regeneration of the endometrium manifest as changes in endometrial epithelialization, glandular regeneration, and vascularization. The mechanisms encompass inflammation, coagulation, and fibrinolytic system balance. However, specific conditions such as endometriosis or TCRA treatment can disrupt the process of cyclical endometrial repair and regeneration. There is uncertainty about traditional clinical treatments' efficacy and side effects, and finding new therapeutic interventions is essential. Researchers have made substantial progress in the perspective of regenerative medicine toward maintaining cyclical endometrial repair and regeneration in recent years. Such progress encompasses the integration of biomaterials, tissue-engineered scaffolds, stem cell therapies, and 3D printing. This review analyzes the mechanisms, diseases, and interventions associated with cyclical endometrial repair and regeneration. The review discusses the advantages and disadvantages of the regenerative interventions currently employed in clinical practice. Additionally, it highlights the significant advantages of regenerative medicine in this domain. Finally, we review stem cells and biologics among the available interventions in regenerative medicine, providing insights into future therapeutic strategies.
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Affiliation(s)
- Xulin Hu
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
- Department of BiotherapyCancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuanChina
| | - Haoming Wu
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | - Xin Yong
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapySichuan UniversityChengduSichuanChina
| | - Yao Wang
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | - Shuhao Yang
- Department of OrthopedicsThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Diyi Fan
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | - Yibo Xiao
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | - Lanyu Che
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | - Kun Shi
- Department of BiotherapyCancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuanChina
| | - Kainan Li
- Clinical Medical College and Affiliated Hospital of Chengdu UniversityChengdu UniversityChengduSichuanChina
| | | | - Huili Zhu
- Department of Reproductive Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of EducationWest China Second University Hospital of Sichuan UniversityChengduSichuanChina
| | - Zhiyong Qian
- Department of BiotherapyCancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuanChina
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Nasiri K, Jahri M, Kolahdouz S, Soleimani M, Makiya A, Saini RS, Merza MS, Yasamineh S, Banakar M, Yazdanpanah MH. MicroRNAs Function in Dental Stem Cells as a Promising Biomarker and Therapeutic Target for Dental Diseases. Mol Diagn Ther 2023; 27:703-722. [PMID: 37773247 DOI: 10.1007/s40291-023-00675-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/23/2023] [Indexed: 10/01/2023]
Abstract
Undifferentiated, highly proliferative, clonogenic, and self-renewing dental stem cells have paved the way for novel approaches to mending cleft palates, rebuilding lost jawbone and periodontal tissue, and, most significantly, recreating lost teeth. New treatment techniques may be guided by a better understanding of these cells and their potential in terms of the specificity of the regenerative response. MicroRNAs have been recognized as an essential component in stem cell biology due to their role as epigenetic regulators of the processes that determine stem cell destiny. MicroRNAs have been proven to be crucial in a wide variety of molecular and biological processes, including apoptosis, cell proliferation, migration, and necrocytosis. MicroRNAs have been recognized to control protein translation, messenger RNA stability, and transcription and have been reported to play essential roles in dental stem cell biology, including the differentiation of dental stem cells, the immunological response, apoptosis, and the inflammation of the dental pulp. Because microRNAs increase dental stem cell differentiation, they may be used in regenerative medicine to either preserve the stem cell phenotype or to aid in the development of tooth tissue. The development of novel biomarkers and therapies for dental illnesses relies heavily on progress made in our knowledge of the roles played by microRNAs in regulating dental stem cells. In this article, we discuss how dental stem cells and their associated microRNAs may be used to cure dental illness.
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Affiliation(s)
- Kamyar Nasiri
- Department of Dentistry, Islamic Azad University, Tehran, Iran
| | - Mohammad Jahri
- Dental Research Center, School of Dentistry, Shahid Beheshti, Research Institute of Dental Sciences, University of Medical Sciences, Tehran, Iran
| | | | | | - Ali Makiya
- Student Research Committee, Faculty of Dentistry, Mashhad University of Medical Science, Mashhad, Iran
| | - Ravinder S Saini
- COAMS, King Khalid University, Abha, 62529, Kingdom of Saudi Arabia
| | - Muna S Merza
- Prosthetic Dental Techniques Department, Al-Mustaqbal University College, Babylon, 51001, Iraq
| | - Saman Yasamineh
- Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran
| | - Morteza Banakar
- Dental Research Center, Dentistry Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Department of Pediatric Dentistry, Faculty of Dentistry, Shahed University, Tehran, Iran.
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Behnam B, Fazilaty H, Ghadyani M, Fadavi P, Taghizadeh-Hesary F. Ciliated, Mitochondria-Rich Postmitotic Cells are Immune-privileged, and Mimic Immunosuppressive Microenvironment of Tumor-Initiating Stem Cells: From Molecular Anatomy to Molecular Pathway. FRONT BIOSCI-LANDMRK 2023; 28:261. [PMID: 37919090 DOI: 10.31083/j.fbl2810261] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 09/15/2023] [Accepted: 10/09/2023] [Indexed: 11/04/2023]
Abstract
Cancer whose major problems are metastasis, treatment resistance, and recurrence is the leading cause of death worldwide. Tumor-initiating stem cells (TiSCs) are a subset of the tumor population responsible for tumor resistance and relapse. Understanding the characteristics and shared features between tumor-initiating stem cells (TiSCs) and long-lived postmitotic cells may hold a key to better understanding the biology of cancer. Postmitotic cells have exited the cell cycle and are transitioned into a non-dividing and terminally differentiated state with a specialized function within a tissue. Conversely, a cancer cell with TiSC feature can divide and produce a variety of progenies, and is responsible for disease progression, tumor resistance to therapy and immune system and disease relapse. Surprisingly, our comprehensive evaluation of TiSCs suggests common features with long-lived post-mitotic cells. They are similar in structure (primary cilia, high mitochondrial content, and being protected by a barrier), metabolism (autophagy and senescence), and function (immunoescape and/or immune-privileged by a blood barrier). In-depth exploration showed how mitochondrial metabolism contributes to these shared features, including high energy demands arising from ciliary and microtubular functionality, increased metabolic activity, and movement. These findings can assist in decoding the remaining properties which offer insights into the biology of TiSCs, with potential implications for enhancing cancer treatment strategies and patient prognosis.
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Affiliation(s)
- Babak Behnam
- Department of Regulatory Affairs, Amarex Clinical Research, NSF International, Germantown, MD 20874, USA
| | - Hassan Fazilaty
- Department of Molecular Life Sciences, University of Zurich, 8057 Zurich, Switzerland
| | - Mobina Ghadyani
- School of Science, Monash University, Melbourne, VIC 3800, Australia
| | - Pedram Fadavi
- Department of Radiation Oncology, Iran University of Medical Sciences, 1445613131 Tehran, Iran
| | - Farzad Taghizadeh-Hesary
- Department of Radiation Oncology, Iran University of Medical Sciences, 1445613131 Tehran, Iran
- ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, 1445613131 Tehran, Iran
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Chudakova DA, Samoilova EM, Chekhonin VP, Baklaushev VP. Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury. Cells 2023; 12:2499. [PMID: 37887343 PMCID: PMC10605572 DOI: 10.3390/cells12202499] [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: 09/27/2023] [Revised: 10/13/2023] [Accepted: 10/18/2023] [Indexed: 10/28/2023] Open
Abstract
Spinal cord injury (SCI) is a medical condition affecting ~2.5-4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed. Recent breakthroughs in stem cell biology and cell reprogramming revolutionized the field. Of them, the use of neural progenitor cells (NPCs) directly reprogrammed from non-neuronal somatic cells without transitioning through a pluripotent state is a particularly attractive strategy. This allows to "scale up" NPCs in vitro and, via their transplantation to the lesion area, partially compensate for the limited regenerative plasticity of the adult spinal cord in humans. As recently demonstrated in non-human primates, implanted NPCs contribute to the functional improvement of the spinal cord after injury, and works in other animal models of SCI also confirm their therapeutic value. However, direct reprogramming still remains a challenge in many aspects; one of them is low efficiency, which prevents it from finding its place in clinics yet. In this review, we describe new insights that recent works brought to the field, such as novel targets (mitochondria, nucleoli, G-quadruplexes, and others), tools, and approaches (mechanotransduction and electrical stimulation) for direct pro-neural reprogramming, including potential ones yet to be tested.
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Affiliation(s)
- Daria A. Chudakova
- Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia
| | - Ekaterina M. Samoilova
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Federal Research and Clinical Center of Specialised Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, Russia
| | - Vladimir P. Chekhonin
- Department of Medical Nanobiotechnology of Medical and Biological Faculty, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia
| | - Vladimir P. Baklaushev
- Federal Center for Brain and Neurotechnologies, Federal Medical and Biological Agency of Russia, 117513 Moscow, Russia
- Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia
- Federal Research and Clinical Center of Specialised Medical Care and Medical Technologies FMBA of Russia, 115682 Moscow, Russia
- Department of Medical Nanobiotechnology of Medical and Biological Faculty, Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, 117997 Moscow, Russia
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Gherghel R, Macovei LA, Burlui MA, Cardoneanu A, Rezus II, Mihai IR, Rezus E. Osteoarthritis—The Role of Mesenchymal Stem Cells in Cartilage Regeneration. APPLIED SCIENCES 2023; 13:10617. [DOI: 10.3390/app131910617] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Osteoarthritis (OA) is a condition that can cause substantial pain, loss of joint function, and a decline in quality of life in patients. Numerous risk factors, including aging, genetics, and injury, have a role in the onset of OA, characterized by structural changes within the joints. Most therapeutic approaches focus on the symptoms and try to change or improve the structure of the joint tissues. Even so, no treatments have been able to stop or slow the progression of OA or give effective and long-lasting relief of symptoms. In the absence of disease-modifying drugs, regenerative medicine is being investigated as a possible treatment that can change the course of OA by changing the structure of damaged articular cartilage. In regenerative therapy for OA, mesenchymal stem cells (MSCs) have been the mainstay of translational investigations and clinical applications. In recent years, MSCs have been discovered to be an appropriate cell source for treating OA due to their ability to expand rapidly in culture, their nontumorigenic nature, and their ease of collection. MSCs’ anti-inflammatory and immunomodulatory capabilities may provide a more favorable local environment for the regeneration of injured articular cartilage, which was thought to be one of the reasons why they were seen as more suited for OA. In addition to bone marrow, MSCs have also been isolated from adipose tissue, synovium, umbilical cord, cord blood, dental pulp, placenta, periosteum, and skeletal muscle. Adipose tissue and bone marrow are two of the most essential tissues for therapeutic MSCs. Positive preclinical and clinical trial results have shown that, despite current limitations and risks, MSC-based therapy is becoming a promising approach to regenerative medicine in treating OA.
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Affiliation(s)
- Robert Gherghel
- Department of Orthopedics and Trauma Surgery, Piatra Neamt Emergency Hospital, 700115 Piatra Neamt, Romania
| | - Luana Andreea Macovei
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Maria-Alexandra Burlui
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Anca Cardoneanu
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Ioana-Irina Rezus
- Department of Dermatology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Ioana Ruxandra Mihai
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
| | - Elena Rezus
- Department of Rheumatology and Rehabilitation, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania
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Fernández-Garza LE, Barrera-Barrera SA, Barrera-Saldaña HA. Mesenchymal Stem Cell Therapies Approved by Regulatory Agencies around the World. Pharmaceuticals (Basel) 2023; 16:1334. [PMID: 37765141 PMCID: PMC10536665 DOI: 10.3390/ph16091334] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 07/02/2023] [Accepted: 07/07/2023] [Indexed: 09/29/2023] Open
Abstract
Cellular therapy has used mesenchymal stem cells (MSCs), which in cell culture are multipotent progenitors capable of producing a variety of cells limited to the mesoderm layer. There are two types of MSC sources: (1) adult MSCs, which are obtained from bone marrow, adipose tissue, peripheral blood, and dental pulp; and (2) neonatal-tissue-derived MSCs, obtained from extra-embryonic tissues such as the placenta, amnion, and umbilical cord. Until April 2023, 1120 registered clinical trials had been using MSC therapies worldwide, but there are only 12 MSC therapies that have been approved by regulatory agencies for commercialization. Nine of the twelve MSC-approved products are from Asia, with Republic of Korea being the country with the most approved therapies. In the future, MSCs will play an important role in the treatment of many diseases. However, there are many issues to deal with before their application and usage in the medical field. Some strategies have been proposed to face these problems with the hope of reaching the objective of applying these MSC therapies at optimal therapeutic levels.
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Affiliation(s)
- Luis E. Fernández-Garza
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
- Departamento de Medicina Interna, Hospital General de Zona con Medicina Familiar No. 2 del Instituto Nacional del Seguro Social, Monterrey 64010, Mexico
| | - Silvia A. Barrera-Barrera
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
| | - Hugo A. Barrera-Saldaña
- Laboratorio Nacional de Servicios Especializados de Investigación, Desarrollo e Innovación de Farmoquímicos y Biotecnológicos (LANSEIDI) del CONACyT, Sede Innbiogem SC, Monterrey 64630, Mexico; (L.E.F.-G.); (S.A.B.-B.)
- Facultades de Medicina y Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66455, Mexico
- Columbia Investigación Científica, Panzacola 62, Colonia Villa Coyoacán, Alcaldía Coyoacán, Ciudad de Mexico 04010, Mexico
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Zeng CW. Advancing Spinal Cord Injury Treatment through Stem Cell Therapy: A Comprehensive Review of Cell Types, Challenges, and Emerging Technologies in Regenerative Medicine. Int J Mol Sci 2023; 24:14349. [PMID: 37762654 PMCID: PMC10532158 DOI: 10.3390/ijms241814349] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Revised: 09/17/2023] [Accepted: 09/19/2023] [Indexed: 09/29/2023] Open
Abstract
Spinal cord injuries (SCIs) can lead to significant neurological deficits and lifelong disability, with far-reaching physical, psychological, and economic consequences for affected individuals and their families. Current treatments for SCIs are limited in their ability to restore function, and there is a pressing need for innovative therapeutic approaches. Stem cell therapy has emerged as a promising strategy to promote the regeneration and repair of damaged neural tissue following SCIs. This review article comprehensively discusses the potential of different stem cell types, such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and neural stem/progenitor cells (NSPCs), in SCI treatment. We provide an in-depth analysis of the unique advantages and challenges associated with each stem cell type, as well as the latest advancements in the field. Furthermore, we address the critical challenges faced in stem cell therapy for SCIs, including safety concerns, ethical considerations, standardization of protocols, optimization of transplantation parameters, and the development of effective outcome measures. We also discuss the integration of novel technologies such as gene editing, biomaterials, and tissue engineering to enhance the therapeutic potential of stem cells. The article concludes by emphasizing the importance of collaborative efforts among various stakeholders in the scientific community, including researchers, clinicians, bioengineers, industry partners, and patients, to overcome these challenges and realize the full potential of stem cell therapy for SCI patients. By fostering such collaborations and advancing our understanding of stem cell biology and regenerative medicine, we can pave the way for the development of groundbreaking therapies that improve the lives of those affected by SCIs.
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Affiliation(s)
- Chih-Wei Zeng
- Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA;
- Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
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Nosrati H, Nosrati M. Artificial Intelligence in Regenerative Medicine: Applications and Implications. Biomimetics (Basel) 2023; 8:442. [PMID: 37754193 PMCID: PMC10526210 DOI: 10.3390/biomimetics8050442] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 09/16/2023] [Accepted: 09/19/2023] [Indexed: 09/28/2023] Open
Abstract
The field of regenerative medicine is constantly advancing and aims to repair, regenerate, or substitute impaired or unhealthy tissues and organs using cutting-edge approaches such as stem cell-based therapies, gene therapy, and tissue engineering. Nevertheless, incorporating artificial intelligence (AI) technologies has opened new doors for research in this field. AI refers to the ability of machines to perform tasks that typically require human intelligence in ways such as learning the patterns in the data and applying that to the new data without being explicitly programmed. AI has the potential to improve and accelerate various aspects of regenerative medicine research and development, particularly, although not exclusively, when complex patterns are involved. This review paper provides an overview of AI in the context of regenerative medicine, discusses its potential applications with a focus on personalized medicine, and highlights the challenges and opportunities in this field.
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Affiliation(s)
- Hamed Nosrati
- Biosensor Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Masoud Nosrati
- Department of Computer Science, Iowa State University, Ames, IA 50011, USA
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Eom YS, Park JH, Kim TH. Recent Advances in Stem Cell Differentiation Control Using Drug Delivery Systems Based on Porous Functional Materials. J Funct Biomater 2023; 14:483. [PMID: 37754897 PMCID: PMC10532449 DOI: 10.3390/jfb14090483] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/14/2023] [Accepted: 09/18/2023] [Indexed: 09/28/2023] Open
Abstract
The unique characteristics of stem cells, which include self-renewal and differentiation into specific cell types, have paved the way for the development of various biomedical applications such as stem cell therapy, disease modelling, and drug screening. The establishment of effective stem cell differentiation techniques is essential for the effective application of stem cells for various purposes. Ongoing research has sought to induce stem cell differentiation using diverse differentiation factors, including chemicals, proteins, and integrin expression. These differentiation factors play a pivotal role in a variety of applications. However, it is equally essential to acknowledge the potential hazards of uncontrolled differentiation. For example, uncontrolled differentiation can give rise to undesirable consequences, including cancerous mutations and stem cell death. Therefore, the development of innovative methods to control stem cell differentiation is crucial. In this review, we discuss recent research cases that have effectively utilised porous functional material-based drug delivery systems to regulate stem cell differentiation. Due to their unique substrate properties, drug delivery systems based on porous functional materials effectively induce stem cell differentiation through the steady release of differentiation factors. These ground-breaking techniques hold considerable promise for guiding and controlling the fate of stem cells for a wide range of biomedical applications, including stem cell therapy, disease modelling, and drug screening.
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Affiliation(s)
| | | | - Tae-Hyung Kim
- School of Integrative Engineering, Chung-Ang University, 84 Heukseuk-ro, Dongjak-gu, Seoul 06974, Republic of Korea; (Y.-S.E.); (J.-H.P.)
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Giordani S, Marassi V, Placci A, Zattoni A, Roda B, Reschiglian P. Field-Flow Fractionation in Molecular Biology and Biotechnology. Molecules 2023; 28:6201. [PMID: 37687030 PMCID: PMC10488451 DOI: 10.3390/molecules28176201] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/08/2023] [Accepted: 08/15/2023] [Indexed: 09/10/2023] Open
Abstract
Field-flow fractionation (FFF) is a family of single-phase separative techniques exploited to gently separate and characterize nano- and microsystems in suspension. These techniques cover an extremely wide dynamic range and are able to separate analytes in an interval between a few nm to 100 µm size-wise (over 15 orders of magnitude mass-wise). They are flexible in terms of mobile phase and can separate the analytes in native conditions, preserving their original structures/properties as much as possible. Molecular biology is the branch of biology that studies the molecular basis of biological activity, while biotechnology deals with the technological applications of biology. The areas where biotechnologies are required include industrial, agri-food, environmental, and pharmaceutical. Many species of biological interest belong to the operational range of FFF techniques, and their application to the analysis of such samples has steadily grown in the last 30 years. This work aims to summarize the main features, milestones, and results provided by the application of FFF in the field of molecular biology and biotechnology, with a focus on the years from 2000 to 2022. After a theoretical background overview of FFF and its methodologies, the results are reported based on the nature of the samples analyzed.
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Affiliation(s)
- Stefano Giordani
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
| | - Valentina Marassi
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
- byFlow srl, 40129 Bologna, Italy
| | - Anna Placci
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
| | - Andrea Zattoni
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
- byFlow srl, 40129 Bologna, Italy
| | - Barbara Roda
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
- byFlow srl, 40129 Bologna, Italy
| | - Pierluigi Reschiglian
- Department of Chemistry “Giacomo Ciamician”, University of Bologna, 40126 Bologna, Italy (V.M.)
- byFlow srl, 40129 Bologna, Italy
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Singh PV, Singh PV, Anjankar A. Harnessing the Therapeutic Potential of Stem Cells in the Management of Chronic Obstructive Pulmonary Disease: A Comprehensive Review. Cureus 2023; 15:e44498. [PMID: 37711945 PMCID: PMC10497883 DOI: 10.7759/cureus.44498] [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: 07/31/2023] [Accepted: 08/31/2023] [Indexed: 09/16/2023] Open
Abstract
Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory condition with limited treatment options. Stem cell therapy has emerged as a promising approach for COPD management due to its regenerative and immunomodulatory properties. This review article aims to comprehensively explore the therapeutic potential of stem cells in COPD management. The introduction provides background on COPD, highlighting its impact on health and the need for novel therapies. The different types of stem cells relevant to COPD, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, are described along with their properties and characteristics. The pathogenesis of COPD is discussed, emphasizing the key mechanisms involved in disease development and progression. Subsequently, the role of stem cells in tissue repair, regeneration, and immunomodulation is examined, highlighting their ability to address specific pathological processes in COPD. Mechanisms of action, such as paracrine signaling, immunomodulation, anti-inflammatory effects, and tissue regeneration, are explored. The interaction between stem cells and the host environment, which promotes lung repair, is also discussed. Challenges in stem cell therapy for COPD, including optimal cell sources, delivery methods, safety, and efficacy, are identified. Regulatory considerations and the importance of standardization are emphasized. Potential strategies for optimizing the therapeutic potential of stem cells in COPD management, such as combination therapies and preconditioning techniques, are outlined. Emerging trends and future directions are highlighted, including advanced cell engineering and patient-specific induced pluripotent stem cells. In conclusion, stem cell therapy holds significant promise for COPD management, addressing the limitations of current treatments. Continued research and development are necessary to overcome challenges, optimize therapies, and realize stem cells' full potential in improving the lives of patients with COPD.
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Affiliation(s)
- Parth V Singh
- Internal Medicine, Indira Gandhi Government Medical College, Nagpur, IND
| | - Prateesh V Singh
- Medicine and Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Ashish Anjankar
- Biochemistry, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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Sahibdad I, Khalid S, Chaudhry GR, Salim A, Begum S, Khan I. Zinc enhances the cell adhesion, migration, and self-renewal potential of human umbilical cord derived mesenchymal stem cells. World J Stem Cells 2023; 15:751-767. [PMID: 37545753 PMCID: PMC10401417 DOI: 10.4252/wjsc.v15.i7.751] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2023] [Revised: 05/15/2023] [Accepted: 06/06/2023] [Indexed: 07/25/2023] Open
Abstract
BACKGROUND Zinc (Zn) is the second most abundant trace element after Fe, present in the human body. It is frequently reported in association with cell growth and proliferation, and its deficiency is considered to be a major disease contributing factor. AIM To determine the effect of Zn on in vitro growth and proliferation of human umbilical cord (hUC)-derived mesenchymal stem cells (MSCs). METHODS hUC-MSCs were isolated from human umbilical cord tissue and characterized based on immunocytochemistry, immunophenotyping, and tri-lineage differentiation. The impact of Zn on cytotoxicity and proliferation was determined by MTT and Alamar blue assay. To determine the effect of Zn on population doubling time (PDT), hUC-MSCs were cultured in media with and without Zn for several passages. An in vitro scratch assay was performed to analyze the effect of Zn on the wound healing and migration capability of hUC-MSCs. A cell adhesion assay was used to test the surface adhesiveness of hUC-MSCs. Transcriptional analysis of genes involved in the cell cycle, proliferation, migration, and self-renewal of hUC-MSCs was performed by quantitative real-time polymerase chain reaction. The protein expression of Lin28, a pluripotency marker, was analyzed by immunocytochemistry. RESULTS Zn at lower concentrations enhanced the rate of proliferation but at higher concentrations (> 100 µM), showed concentration dependent cytotoxicity in hUC-MSCs. hUC-MSCs treated with Zn exhibited a significantly greater healing and migration rate compared to untreated cells. Zn also increased the cell adhesion rate, and colony forming efficiency (CFE). In addition, Zn upregulated the expression of genes involved in the cell cycle (CDC20, CDK1, CCNA2, CDCA2), proliferation (transforming growth factor β1, GDF5, hypoxia-inducible factor 1α), migration (CXCR4, VCAM1, VEGF-A), and self-renewal (OCT4, SOX2, NANOG) of hUC-MSCs. Expression of Lin28 protein was significantly increased in cells treated with Zn. CONCLUSION Our findings suggest that zinc enhances the proliferation rate of hUC-MSCs decreasing the PDT, and maintaining the CFE. Zn also enhances the cell adhesion, migration, and self-renewal of hUC-MSCs. These results highlight the essential role of Zn in cell growth and development.
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Affiliation(s)
- Iqra Sahibdad
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Shumaila Khalid
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - G Rasul Chaudhry
- Department of Biological Sciences, Oakland University, Rochester, MI 48309, United States
| | - Asmat Salim
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Sumreen Begum
- Stem Cell Research Laboratory (SCRL), Sindh Institute of Urology and Transplantation (SIUT), Karachi 74200, Sindh, Pakistan
| | - Irfan Khan
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Sindh, Pakistan.
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Go YY, Lee CM, Chae SW, Song JJ. Regenerative capacity of trophoblast stem cell-derived extracellular vesicles on mesenchymal stem cells. Biomater Res 2023; 27:62. [PMID: 37370189 DOI: 10.1186/s40824-023-00396-5] [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: 03/16/2023] [Accepted: 05/16/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Human mesenchymal stem cells (MSCs) are therapeutic for clinical applications because of their excellent immunomodulatory and multiple lineage differentiation abilities at tissue injury sites. However, insufficient number of cells and lack of regenerative properties during in vitro expansion still limit the clinical applicability of MSC therapies. Here, we demonstrated a preconditioning strategy with trophoblast stem cell-derived extracellular vesicles (TSC-EVs) to boost the proliferation and regenerative capacity of MSCs. METHODS We employed cell proliferation analyses such as CCK8 and BrdU assays to determine the proliferation-promoting role of TSC-EVs on MSCs. Osteogenic effects of TSC-EVs on MSCs were assessed by alkaline phosphatase (ALP) activity, calcium assays, and calvarial bone defect animal models. For skin regenerative effects, skin wound mice model was exploited to analyze wound-healing rate in this study, as well as immunofluorescence and histological staining evaluates. We also performed the small RNA profiling and RNA-sequencing analyzes to understand the cellular mechanism of TSC-EVs on MSCs. RESULTS TSC-EVs significantly promoted MSC proliferation under xeno-free conditions and facilitated the therapeutic effects of MSCs, including osteogenesis, anti-senescence, and wound healing. Transcriptomic analysis also provided evidence that specific microRNAs in TSC-EVs and differentially expressed genes (DEGs) in TSC-EV-treated MSCs showed the possibility of TSC-EVs triggering the regenerative abilities of MSCs with cytokine interaction. Hence, we found that NGF/Akt signaling mediated the regenerative effects of TSC-EVs on MSCs as a particular cellular signaling pathway. CONCLUSION The results of this study demonstrated the functional properties of TSC-EVs on MSCs for MSC-based therapeutic applications, suggesting that TSC-EVs may serve as a potential preconditioning source for MSC therapy in the clinical field of regenerative medicine.
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Affiliation(s)
- Yoon-Young Go
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea
- Institute for Health Care Convergence Center, Korea University Guro Hospital, Seoul, 08308, Republic of Korea
| | - Chan-Mi Lee
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea
| | - Sung-Won Chae
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea
| | - Jae-Jun Song
- Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Guro Hospital, 80 Guro-Dong, Guro-Gu, Seoul, 08308, South Korea.
- Institute for Health Care Convergence Center, Korea University Guro Hospital, Seoul, 08308, Republic of Korea.
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Pizzuti V, Paris F, Marrazzo P, Bonsi L, Alviano F. Mitigating Oxidative Stress in Perinatal Cells: A Critical Step toward an Optimal Therapeutic Use in Regenerative Medicine. Biomolecules 2023; 13:971. [PMID: 37371551 DOI: 10.3390/biom13060971] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/26/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
Oxidative stress (OS) occurs when the production of reactive oxygen species (ROS) is not balanced by the body's antioxidant defense system. OS can profoundly affect cellular health and function. ROS can have a profound negative impact on cells that undergo a predestined and time-regulated process of proliferation or differentiation, such as perinatal stem cells. Due to the large-scale employment of these immunotolerant stem cells in regenerative medicine, it is important to reduce OS to prevent them from losing function and increase their application in the regenerative medicine field. This goal can be achieved through a variety of strategies, such as the use of antioxidants and other compounds that can indirectly modulate the antioxidant defense system by enhancing cellular stress response pathways, including autophagy and mitochondrial function, thereby reducing ROS levels. This review aims to summarize information regarding OS mechanisms in perinatal stem cells and possible strategies for reducing their deleterious effects.
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Affiliation(s)
- Valeria Pizzuti
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Francesca Paris
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Pasquale Marrazzo
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Laura Bonsi
- Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy
| | - Francesco Alviano
- Department of Biomedical and Neuromotor Science, University of Bologna, 40126 Bologna, Italy
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Tian Z, Yu T, Liu J, Wang T, Higuchi A. Introduction to stem cells. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2023; 199:3-32. [PMID: 37678976 DOI: 10.1016/bs.pmbts.2023.02.012] [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: 03/17/2023]
Abstract
Stem cells have self-renewal capability and can proliferate and differentiate into a variety of functionally active cells that can serve in various tissues and organs. This review discusses the history, definition, and classification of stem cells. Human pluripotent stem cells (hPSCs) mainly include embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Embryonic stem cells are derived from the inner cell mass of the embryo. Induced pluripotent stem cells are derived from reprogramming somatic cells. Pluripotent stem cells have the ability to differentiate into cells derived from all three germ layers (endoderm, mesoderm, and ectoderm). Adult stem cells can be multipotent or unipotent and can produce tissue-specific terminally differentiated cells. Stem cells can be used in cell therapy to replace and regenerate damaged tissues or organs.
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Affiliation(s)
- Zeyu Tian
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
| | - Tao Yu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
| | - Jun Liu
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China
| | - Ting Wang
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
| | - Akon Higuchi
- State Key Laboratory of Ophthalmology, Optometry and Visual Science, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China; Department of Chemical and Materials Engineering, National Central University, Jhongli, Taoyuan, Taiwan.
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Samadi A, Moammeri A, Pourmadadi M, Abbasi P, Hosseinpour Z, Farokh A, Shamsabadipour A, Heydari M, Mohammadi MR. Cell Encapsulation and 3D Bioprinting for Therapeutic Cell Transplantation. ACS Biomater Sci Eng 2023; 9:1862-1890. [PMID: 36877212 DOI: 10.1021/acsbiomaterials.2c01183] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/07/2023]
Abstract
The promise of cell therapy has been augmented by introducing biomaterials, where intricate scaffold shapes are fabricated to accommodate the cells within. In this review, we first discuss cell encapsulation and the promising potential of biomaterials to overcome challenges associated with cell therapy, particularly cellular function and longevity. More specifically, cell therapies in the context of autoimmune disorders, neurodegenerative diseases, and cancer are reviewed from the perspectives of preclinical findings as well as available clinical data. Next, techniques to fabricate cell-biomaterials constructs, focusing on emerging 3D bioprinting technologies, will be reviewed. 3D bioprinting is an advancing field that enables fabricating complex, interconnected, and consistent cell-based constructs capable of scaling up highly reproducible cell-biomaterials platforms with high precision. It is expected that 3D bioprinting devices will expand and become more precise, scalable, and appropriate for clinical manufacturing. Rather than one printer fits all, seeing more application-specific printer types, such as a bioprinter for bone tissue fabrication, which would be different from a bioprinter for skin tissue fabrication, is anticipated in the future.
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Affiliation(s)
- Amirmasoud Samadi
- Department of Chemical and Biomolecular Engineering, 6000 Interdisciplinary Science & Engineering Building (ISEB), Irvine, California 92617, United States
| | - Ali Moammeri
- School of Chemical Engineering, College of Engineering, University of Tehran, Enghelab Square, 16 Azar Street, Tehran 1417935840, Iran
| | - Mehrab Pourmadadi
- School of Chemical Engineering, College of Engineering, University of Tehran, Enghelab Square, 16 Azar Street, Tehran 1417935840, Iran
| | - Parisa Abbasi
- Department of Chemical and Petroleum Engineering, Sharif University of Technology, Azadi Avenue, Tehran 1458889694, Iran
| | - Zeinab Hosseinpour
- Biotechnology Research Laboratory, Faculty of Chemical Engineering, Babol Noshirvani University of Technology, Babol 4714871167, Mazandaran Province, Iran
| | - Arian Farokh
- School of Chemical Engineering, College of Engineering, University of Tehran, Enghelab Square, 16 Azar Street, Tehran 1417935840, Iran
| | - Amin Shamsabadipour
- School of Chemical Engineering, College of Engineering, University of Tehran, Enghelab Square, 16 Azar Street, Tehran 1417935840, Iran
| | - Maryam Heydari
- Department of Cell and Molecular Biology, Faculty of Biological Science, University of Kharazmi, Tehran 199389373, Iran
| | - M Rezaa Mohammadi
- Dale E. and Sarah Ann Fowler School of Engineering, Chapman University, Orange, California 92866, United States
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Cell-Free Therapies: The Use of Cell Extracts to Mitigate Irradiation-Injured Salivary Glands. BIOLOGY 2023; 12:biology12020305. [PMID: 36829582 PMCID: PMC9953449 DOI: 10.3390/biology12020305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Revised: 02/06/2023] [Accepted: 02/07/2023] [Indexed: 02/17/2023]
Abstract
Radiotherapy is a standard treatment for head and neck cancer patients worldwide. However, millions of patients who received radiotherapy consequently suffer from xerostomia because of irreversible damage to salivary glands (SGs) caused by irradiation (IR). Current treatments for IR-induced SG hypofunction only provide temporary symptom alleviation but do not repair the damaged SG, thus resulting in limited treatment efficacy. Therefore, there has recently been a growing interest in regenerative treatments, such as cell-free therapies. This review aims to summarize cell-free therapies for IR-induced SG, with a particular emphasis on utilizing diverse cell extract (CE) administrations. Cell extract is a group of heterogeneous mixtures containing multifunctional inter-cellular molecules. This review discusses the current knowledge of CE's components and efficacy. We propose optimal approaches to improve cell extract treatment from multiple perspectives (e.g., delivery routes, preparation methods, and other details regarding CE administration). In addition, the advantages and limitations of CE treatment are systematically discussed by comparing it to other cell-free (such as conditioned media and exosomes) and cell-based therapies. Although a comprehensive identification of the bioactive factors within CEs and their mechanisms of action have yet to be fully understood, we propose cell extract therapy as an effective, practical, user-friendly, and safe option to conventional therapies in IR-induced SG.
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50
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Wang B, Gao W, Zheng MY, Lin G, Lue TF. Recent advances in stem cell therapy for erectile dysfunction: a narrative review. Expert Opin Biol Ther 2023; 23:565-573. [PMID: 37078259 PMCID: PMC10330142 DOI: 10.1080/14712598.2023.2203811] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 04/13/2023] [Indexed: 04/21/2023]
Abstract
INTRODUCTION While phosphodiesterase type 5 inhibitors (PDE5is) and others are used to treat Erectile dysfunction (ED), many patients are either unresponsive or resistant to it. Stem cell therapy (SCT) is a promising alternative approach. Numerous preclinical trials have demonstrated improved erectile function in animal models using SCT, although the number of clinical trials investigating SCT for men with ED is limited. Nonetheless, findings from human clinical trials suggest that SCT may be a useful treatment option. AREAS COVERED Biomedical literature, including PubMed, ClinicalTrials.gov, and European Union Clinical Trials Registry, were analyzed to summarize and synthesize information on stem cell therapy for ED in this narrative review. The achievements in preclinical and clinical evaluations are presented and critically analyzed. EXPERT OPINION SCT has demonstrated some benefits in improving erectile function, while further studies are urgently needed. Such studies would provide valuable insights into the optimal use of stem cell therapy and its potential as a therapeutic option for ED. Taking advantage of different mechanisms of action involved in various regenerative therapies, combination therapies such as SCT and low-energy shock waves or platelet-rich plasma may provide a more effective therapy and warrant further research.
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Affiliation(s)
- Bohan Wang
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
- Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Wenjun Gao
- Department of Urology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Micha Y. Zheng
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
| | - Guiting Lin
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
| | - Tom F Lue
- Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA
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