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Rahnama M, Ghasemzadeh N, Latifi Z, Kheradmand F, Koukia FA, Khan S, Golchin A. Menstrual blood and endometrial mesenchymal stem/stromal cells: A frontier in regenerative medicine and cancer therapy. Eur J Pharmacol 2025; 1000:177726. [PMID: 40350020 DOI: 10.1016/j.ejphar.2025.177726] [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: 12/24/2024] [Revised: 05/08/2025] [Accepted: 05/09/2025] [Indexed: 05/14/2025]
Abstract
The acquisition of suitable stem cell sources is a significant issue in regenerative medicine. There has been considerable interest in utilizing mesenchymal stem cells (MSCs) derived from endometrial and menstrual blood as a promising resource of MSCs, owing to their unique biochemical properties and prospective use in clinical therapies. This population of stem cells has distinct characteristics in terms of immunophenotype, proliferation rate, and differentiation capacity. A notable characteristic of these stem cells is their capacity to develop into mesodermal lineages, highlighting their regenerative capability. Moreover, the presence of certain surface markers facilitates the augmentation of clonogenic endometrial MSCs. Their distinctive characteristics, along with their swift multiplication ability, underscore their significant promise for therapeutic applicability in regenerative medicine and cell-based treatments. Current investigations are examining possible usage of diverse stem cell resources in the treatment of inflammatory diseases and perhaps intractable illnesses like Parkinson's disease, utilizing their immunomodulatory properties. This review aims to analyze stem cell-related research that has utilized endometrial and menstrual blood-derived MSCs (enMSCs and MenSCs) with a special focus on their clinical application. We will explore the existing evidence about the therapeutic potential for these stem cells across many medical diseases and address the obstacles and prospective trajectories in this domain. Additionally, we will study the unique properties of enMSCs and MenSCs that make them promising candidates for regenerative medicine.
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Affiliation(s)
- Maryam Rahnama
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran; Department of Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Navid Ghasemzadeh
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran; Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Zeinab Latifi
- Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Fatemeh Kheradmand
- Department of Clinical Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Fariba Abbasi Koukia
- Department of Pathology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Sharun Khan
- Graduate Institute of Medicine, Yuan Ze University, Taoyuan 32003, Taiwan
| | - Ali Golchin
- Department of Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran; Independent Researcher, Urmia, Iran.
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Che H, Hart ML, Lauer JC, Selig M, Voelker M, Kurz B, Rolauffs B. A xenogenic-free culture medium for cell micro-patterning systems as cell-instructive biomaterials for potential clinical applications. Biomed Mater 2025; 20:025008. [PMID: 39719129 DOI: 10.1088/1748-605x/ada335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 12/24/2024] [Indexed: 12/26/2024]
Abstract
Cell micro-patterning controls cell fate and function and has potential for generating therapeutically usable mesenchymal stromal cell (MSC) populations with precise functions. However, to date, the micro-patterning of human cells in a translational context has been impossible because only ruminant media supplements, e.g. fetal bovine serum (FBS), are established for use with micro-patterns (MPs). Thus, there are currently no good manufacturing practice (GMP)-compliant media available for MPs. This study tested a xenogenic-free human plasma and platelet lysate (hP + PL) medium supplement to determine its compatibility with MPs. Unfiltered hP + PL medium resulted in significant protein deposition, creating a 'carpet-like' layer that rendered MPs ineffective. Filtration (3×/5×) eliminated this effect. Importantly, quantitative comparison using droplet digital PCR revealed that human MSCs in all media types exhibited similar profiles with strong myogenic Calponin 1/Transgelin 2 (TAGLN2) and weaker osteogenic alkaline phosphatase/Runt-related transcription factor 2 marker expression, and much weaker adipogenic (lipoprotein lipase/peroxisome proliferator-activated receptor gamma) and chondrogenic (collagen type II/aggrecan) expression, with profiles being dominated by myogenic markers. Within these similar profiles, an even stronger induction of the myogenic marker TAGLN2 by all hP + PL- compared to FBS-containing media. Overall, this suggested that FBS can be replaced with hP + PL without altering differentiation profiles. However, assessing individual MSC responses to various MP types with defined categories revealed that unfiltered hP + PL medium was unusable. Importantly, FBS- and 3× filtered hP + PL media were comparable in each differentiation category. Summarized, this study recommends 3× filtered hP + PL as a xenogenic-free and potentially GMP-compliant alternative to FBS as a culture medium supplement for micro-patterning cell populations in both basic and translational research that will ensure consistent and reliable MSC micro-patterning for therapeutic use.
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Affiliation(s)
- Hui Che
- Orthopedics and Sports Medicine Center, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, People's Republic of China
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
| | - Melanie L Hart
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
| | - Jasmin C Lauer
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
| | - Mischa Selig
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
| | - Marita Voelker
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
| | - Bodo Kurz
- Department of Anatomy, Christian-Albrechts-University, Otto-Hahn-Platz 8, 24118 Kiel, Germany
| | - Bernd Rolauffs
- G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79108 Freiburg im Breisgau, Germany
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Lu ZJ, Gu HY, Li ZQ, Lin FX. Low frequency‑pulsed electromagnetic fields promote osteogenic differentiation of bone marrow‑derived mesenchymal stem cells by regulating connexin 43 expression. Exp Ther Med 2024; 28:446. [PMID: 39386938 PMCID: PMC11462399 DOI: 10.3892/etm.2024.12736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 08/22/2024] [Indexed: 10/12/2024] Open
Abstract
The present study investigated the effect of connexin 43 (Cx43) on the regulation of osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) using low-frequency-pulsed electromagnetic fields (LPEMF). The BMSCs were isolated and cultured in vitro using adherent whole-bone marrow cultures. CCK-8 assay was used to detect the effects of LPEMF on the proliferation ability of BMSCs and alkaline phosphatase (ALP) activity and the levels of osteogenic marker genes were detected to evaluate the osteogenic ability change following LPEMF treatment. Lentiviral vector-mediated RNA interference was transfected into BMSCs to inhibit the expression of Cx43 and western blotting was used to detect Cx43 expression. The BMSCs showed the highest proliferation following LPEMF treatment at 80 Hz for 1 h. The results of ALP activity, osteogenic marker genes and Alizarin Red S staining showed that the osteogenic ability was notably increased following LPEMF treatment at 80 Hz for 1 h. Cx43 expression increased during the osteogenic differentiation of BMSCs following LPEMF treatment at 80 Hz. The enhanced osteogenic differentiation of the LPEMF-treated BMSCs were partially reversed when Cx43 expression was inhibited. LPEMF may promote the osteogenic differentiation of BMSCs by regulating Cx43 expression and enhancing osteogenic ability.
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Affiliation(s)
- Zhi-Jun Lu
- Department of Spine Surgery, Ganzhou People's Hospital (The Affiliated Ganzhou Hospital of Jiangxi Medical College of Nanchang University, Ganzhou Hospital-Nanfang Hospital of Southern Medical University), Ganzhou, Jiangxi 341000, P.R. China
| | - Hou-Yun Gu
- Department of Spine Surgery, Ganzhou People's Hospital (The Affiliated Ganzhou Hospital of Jiangxi Medical College of Nanchang University, Ganzhou Hospital-Nanfang Hospital of Southern Medical University), Ganzhou, Jiangxi 341000, P.R. China
| | - Zhi-Qiang Li
- Department of Spine Surgery, Ganzhou People's Hospital (The Affiliated Ganzhou Hospital of Jiangxi Medical College of Nanchang University, Ganzhou Hospital-Nanfang Hospital of Southern Medical University), Ganzhou, Jiangxi 341000, P.R. China
| | - Fei-Xiang Lin
- Department of Spine Surgery, Ganzhou People's Hospital (The Affiliated Ganzhou Hospital of Jiangxi Medical College of Nanchang University, Ganzhou Hospital-Nanfang Hospital of Southern Medical University), Ganzhou, Jiangxi 341000, P.R. China
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Son KH, Kim DH, Park S, Kim HJ, Park M, Kim SJ, Lee SJ, Ahn K, Lee JW. Spherical Shell Bioprinting to Produce Uniform Spheroids with Controlled Sizes. J Funct Biomater 2024; 15:350. [PMID: 39590553 PMCID: PMC11595458 DOI: 10.3390/jfb15110350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 11/14/2024] [Accepted: 11/16/2024] [Indexed: 11/28/2024] Open
Abstract
Conventional cell spheroid production methods are largely manual, leading to variations in size and shape that compromise consistency and reliability for use in cell-based therapeutic applications. To enhance spheroid production, a spherical shell bioprinting system was implemented, enabling the high-throughput generation of uniform cell spheroids with precisely controlled sizes. The system encapsulates cells within thin alginate hydrogel shells formed through bioprinting and ion crosslinking reactions. Alginate-calcium ion crosslinking created alginate shells that contained gelatin-based bioinks with embedded cells, facilitating spontaneous cell aggregation within the shells and eliminating the need for plastic wells. By adjusting cell concentrations in the alginate-gelatin bioink, we achieved precise control over spheroid size, maintaining a sphericity above 0.94 and size deviations within ±10 µm. This method has been successfully applied to various cell types including cancer cells, fibroblasts, chondrocytes, and epithelial cells, demonstrating its versatility. This scalable approach enhances the reliability of cell therapy and drug screening, offering a robust platform for future biomedical applications.
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Affiliation(s)
- Kuk Hui Son
- Department of Thoracic and Cardiovascular Surgery, Gil Medical Center, College of Medicine, Gachon University, 21, Namdong-daero 774 Beon-gil, Namdong-gu, Incheon 21565, Republic of Korea;
| | - Dong-Ha Kim
- Research Institute, Sphebio Co., Ltd., 501-ho, 3, Achasan-ro 11ga-gil, Seongdong-gu, Seoul 04796, Republic of Korea; (D.-H.K.); (H.J.K.); (M.P.); (S.-J.K.)
| | - Seunghye Park
- Department of Health Sciences and Technology, GAIHST, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Republic of Korea;
| | - Hyun Jae Kim
- Research Institute, Sphebio Co., Ltd., 501-ho, 3, Achasan-ro 11ga-gil, Seongdong-gu, Seoul 04796, Republic of Korea; (D.-H.K.); (H.J.K.); (M.P.); (S.-J.K.)
| | - Mira Park
- Research Institute, Sphebio Co., Ltd., 501-ho, 3, Achasan-ro 11ga-gil, Seongdong-gu, Seoul 04796, Republic of Korea; (D.-H.K.); (H.J.K.); (M.P.); (S.-J.K.)
| | - Seung-Jin Kim
- Research Institute, Sphebio Co., Ltd., 501-ho, 3, Achasan-ro 11ga-gil, Seongdong-gu, Seoul 04796, Republic of Korea; (D.-H.K.); (H.J.K.); (M.P.); (S.-J.K.)
| | - Sang Jin Lee
- Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157, USA;
| | - Keunsun Ahn
- Research Institute, Sphebio Co., Ltd., 501-ho, 3, Achasan-ro 11ga-gil, Seongdong-gu, Seoul 04796, Republic of Korea; (D.-H.K.); (H.J.K.); (M.P.); (S.-J.K.)
| | - Jin Woo Lee
- Department of Health Sciences and Technology, GAIHST, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Republic of Korea;
- Department of Molecular Medicine, College of Medicine, Gachon University, 155, Gaetbeol-ro, Yeonsu-ku, Incheon 21999, Republic of Korea
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Looi CK, Loo EM, Lim HC, Chew YL, Chin KY, Cheah SC, Goh BH, Mai CW. Revolutionizing the treatment for nasopharyngeal cancer: the impact, challenges and strategies of stem cell and genetically engineered cell therapies. Front Immunol 2024; 15:1484535. [PMID: 39450176 PMCID: PMC11499120 DOI: 10.3389/fimmu.2024.1484535] [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: 08/22/2024] [Accepted: 09/24/2024] [Indexed: 10/26/2024] Open
Abstract
Nasopharyngeal carcinoma (NPC) is a distinct malignancy of the nasopharynx and is consistently associated with the Epstein-Barr virus (EBV) infection. Its unique anatomical location and complex aetiology often result in advanced-stage disease at first diagnosis. While radiotherapy (RT) and chemotherapy have been the mainstays of treatment, they often fail to prevent tumour recurrence and metastasis, leading to high rates of treatment failure and mortality. Recent advancement in cell-based therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown great promise in hematological malignancies and are now being investigated for NPC. However, challenges such as targeting specific tumour antigens, limited T cell persistence and proliferation, and managing treatment-related toxicities must be addressed. Extensive research is needed to enhance the effectiveness and safety of these therapies, paving the way for their integration into standard clinical practice for better management of NPC and a better quality of life for human health.
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Affiliation(s)
- Chin-King Looi
- School of Postgraduate Studies, International Medical University, Kuala Lumpur, Malaysia
| | - Ee-Mun Loo
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
- Advanced Genomics Laboratory, AGTC Genomics, Kuala Lumpur, Malaysia
| | - Heng-Chee Lim
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
| | - Yik-Ling Chew
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
| | - Kok-Yong Chin
- Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia
| | - Shiau-Chuen Cheah
- Faculty of Medicine and Health Sciences, UCSI University, Port Dickson, Negeri Sembilan, Malaysia
| | - Bey Hing Goh
- Sunway Biofunctional Molecules Discovery Centre, School of Medical and Life Sciences, Sunway University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia
- Biofunctional Molecule Exploratory Research Group, School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor Darul Ehsan, Malaysia
- College of Pharmaceutical Sciences, Zhejiang University, Zhejiang, China
| | - Chun-Wai Mai
- Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia
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Costa CMM, Santos DS, Opretzka LCF, de Assis Silva GS, Santos GC, Evangelista AF, Soares MBP, Villarreal CF. Different mechanisms guide the antinociceptive effect of bone marrow-mononuclear cells and bone marrow-mesenchymal stem/stromal cells in trigeminal neuralgia. Life Sci 2024; 354:122944. [PMID: 39111567 DOI: 10.1016/j.lfs.2024.122944] [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: 05/20/2024] [Revised: 07/21/2024] [Accepted: 08/04/2024] [Indexed: 08/10/2024]
Abstract
AIMS Trigeminal neuralgia (TN) is a type of chronic orofacial pain evoked by trivial stimuli that manifests as episodes of excruciating and sudden, recurrent paroxysmal pain. Most patients are refractory to pharmacological therapy used for the treatment of TN. Mononuclear cells (MNC) and mesenchymal stem/stromal cells (MSC) have shown therapeutic potential in painful neuropathies, but their mechanism of action is not fully understood. The present work aimed to investigate the antinociceptive effect and mechanism of action of MNC and MSC in experimental TN. MATERIALS AND METHODS Mice submitted to the chronic constriction injury of the infraorbital nerve (CCI-ION) mouse model of TN received a single intravenous injection of saline, MNC, or MSC (1 × 106 cells/mouse). The effect of the treatments on the behavioral signs of painful neuropathy, morphological aspects of the infraorbital nerve, and inflammatory and oxidative stress markers in the infraorbital nerve were assessed. KEY FINDINGS MNC and MSC improved behavioral painful neuropathy, activated key cell signaling antioxidant pathways by increasing Nrf2 expression, and reduced the proinflammatory cytokines IL-1β and TNF-α. However, treatment with MSC, but not MNC, was associated with a sustained increase of IL-10 and with the re-establishment of the morphometric pattern of the infraorbital nerve, indicating a difference in the mechanism of action between MNC and MSC. In line with this result, in IL-10 knockout mice, MSC transplantation did not induce an antinociceptive effect. SIGNIFICANCE Importantly, these data suggest an IL-10-induced disease-modifying profile related to MSC treatment and reinforce cell therapy's potential in treating trigeminal neuralgia.
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Affiliation(s)
| | | | | | | | - Girlaine Café Santos
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil.
| | | | - Milena Botelho Pereira Soares
- Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil; Institute of Advanced Systems in Health, SENAI CIMATEC, Salvador 41650-010, BA, Brazil.
| | - Cristiane Flora Villarreal
- Faculty of Pharmacy, Federal University of Bahia, Salvador 40170-115, BA, Brazil; Gonçalo Moniz Institute, Oswaldo Cruz Foundation (FIOCRUZ), Salvador 40296-710, BA, Brazil.
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Jaber M, Alshikh Ali AM, El Saleh RI, Prasad P. The Use of Stem Cells in Bone Regeneration of Cleft Lip and Palate Patients: A Systematic Review. J Clin Med 2024; 13:5315. [PMID: 39274529 PMCID: PMC11396532 DOI: 10.3390/jcm13175315] [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: 07/29/2024] [Revised: 08/25/2024] [Accepted: 09/05/2024] [Indexed: 09/16/2024] Open
Abstract
Background and Objectives: Cleft lip alone or a combination of cleft lip and palate (CLP) is a common developmental abnormality in the craniofacial region. This umbrella review aims to identify promising avenues for treatment using stem cell therapy. Materials and Methods: Systematic reviews from 2014 to 2024 were searched among databases like PubMed, Medline, and Google Scholar. PRISMA guidelines were employed to ensure the thoroughness of the search. A quality assessment (ROBIS) of the included reviews was conducted to ensure the reliability and validity of the synthesized evidence. Results: Five systematic reviews were selected for this umbrella review. Results show that stem cell therapy, specifically using mesenchymal stem cells (MSCs) and adipocyte stem cells (ADSCs), promotes bone regeneration in CLP deformities. Although multiple studies have established the effectiveness of diverse types of stem cells in treating CLP, important considerations including safety concerns, methodological variability, and the need for standardization have been identified. The fact that the number of relevant systematic reviews that matched our inclusion criteria was limited could affect this research's robustness and may limit the breadth and depth of evidence synthesis. Definitive conclusions could not be reached due to variation among treatments and outcomes. Conclusions: The examined studies highlight the potential of stem cell therapy as a complementary approach to existing treatments for CLP. However, there are challenges that need to be addressed, including concerns regarding safety, variations in methodologies, and the need for standardization. Exploring the potential of other stem cell types may further enhance treatment outcomes for CLP patients.
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Affiliation(s)
- Mohamed Jaber
- Department of Clinical Dental Sciences, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab Emirates
- Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | | | - Roba Imad El Saleh
- Interns, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Prathibha Prasad
- Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
- Department of Basic Medical and Dental Sciences, College of Dentistry, Ajman University, Ajman P.O. Box 346, United Arab Emirates
- Department of Oral Pathology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Saveetha University, Chennai 600077, India
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Shah S, Ghosh D, Otsuka T, Laurencin CT. Classes of Stem Cells: From Biology to Engineering. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2024; 10:309-322. [PMID: 39387056 PMCID: PMC11463971 DOI: 10.1007/s40883-023-00317-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 06/30/2023] [Accepted: 08/16/2023] [Indexed: 10/12/2024]
Abstract
Purpose The majority of adult tissues are limited in self-repair and regeneration due to their poor intrinsic regenerative capacity. It is widely recognized that stem cells are present in almost all adult tissues, but the natural regeneration in adult mammals is not sufficient to recover function after injury or disease. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth fully engineered class: the synthetic artificial stem cell (SASC). This review aims to discuss the applications of these stem cell classes in musculoskeletal regenerative engineering. Method We screened articles in PubMed and bibliographic search using a combination of keywords. Relevant and high-cited articles were chosen for inclusion in this narrative review. Results In this review, we discuss the different classes of stem cells that are biologically derived (ESCs and MSCs) or semi-engineered/engineered (iPSCs, SASC). We also discuss the applications of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of the classes and how they impact the clinical translation of these therapies. Conclusion Each class of stem cells has advantages and disadvantages in preclinical and clinical settings. We also propose the engineered SASC class as a potentially disease-modifying therapy that harnesses the paracrine action of biologically derived stem cells to mimic regenerative potential. Lay Summary The majority of adult tissues are limited in self-repair and regeneration, even though stem cells are present in almost all adult tissues. Historically, 3 classes of stem cells have been defined: embryonic stem cells (ESCs), adult mesenchymal stem cells (MSCs), and induced pluripotent stem cells (iPSCs). Here, we have defined a fourth, fully engineered class: the synthetic artificial stem cell (SASC). In this review, we discuss the applications of each of these stem cell classes in musculoskeletal regenerative engineering. We further summarize the advantages and disadvantages of using each of these classes and how they impact the clinical translation of these therapies.
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Affiliation(s)
- Shiv Shah
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030-3711, USA
- Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA
| | - Debolina Ghosh
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030-3711, USA
| | - Takayoshi Otsuka
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030-3711, USA
- Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA
| | - Cato T. Laurencin
- The Cato T. Laurencin Institute for Regenerative Engineering, University of Connecticut, 263 Farmington Avenue, Farmington, CT 06030-3711, USA
- Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, CT, USA
- Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT, USA
- Department of Orthopedic Surgery, University of Connecticut Health, Farmington, CT, USA
- Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA
- Department of Materials Science and Engineering, University of Connecticut, Storrs, CT, USA
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Maria OM, Heram A, Tran SD. Bioengineering from the laboratory to clinical translation in oral and maxillofacial reconstruction. Saudi Dent J 2024; 36:955-962. [PMID: 39035556 PMCID: PMC11255950 DOI: 10.1016/j.sdentj.2024.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 05/07/2024] [Accepted: 05/07/2024] [Indexed: 07/23/2024] Open
Abstract
Background Conventional techniques used in oral and maxillofacial reconstruction focus mainly on utilizing autologous tissues that have unquestionably improved function and esthetics for many patients, worldwide. However, the success depends on countless factors such as: donor and recipient sites conditions, patient's medical history, surgeon's experience, restricted availability of high-quality autogenous tissues or stem cells, and increased surgical cost and time. Materials and Methods Lately, teaming researchers, scientists, surgeons, and engineers, to address these limitations, have allowed tremendous progress in recombinant protein therapy, cell-based therapy, and gene therapy. Results Over the past few years, biomedical engineering has been evolving from the laboratory to clinical applications, for replacement of damaged body tissues due to trauma, cancer, congenital or acquired disorders. Conclusions This review provides an outlook on the content, benefits, recent advances, limitations, and future expectations of biomedical engineering for salivary glands, oral mucosa, dental structures, and maxillofacial reconstruction.
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Affiliation(s)
- Ola M. Maria
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Ashraf Heram
- Grand Strand Facial and Jaw Surgery, Myrtle Beach, SC, United States
| | - Simon D. Tran
- Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, Quebec, Canada
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Da Silva D, Crous A, Abrahamse H. Enhancing Osteoblast Differentiation from Adipose-Derived Stem Cells Using Hydrogels and Photobiomodulation: Overcoming In Vitro Limitations for Osteoporosis Treatment. Curr Issues Mol Biol 2024; 46:6346-6365. [PMID: 39057021 PMCID: PMC11276038 DOI: 10.3390/cimb46070379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 06/18/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Osteoporosis represents a widespread and debilitating chronic bone condition that is increasingly prevalent globally. Its hallmark features include reduced bone density and heightened fragility, which significantly elevate the risk of fractures due to the decreased presence of mature osteoblasts. The limitations of current pharmaceutical therapies, often accompanied by severe side effects, have spurred researchers to seek alternative strategies. Adipose-derived stem cells (ADSCs) hold considerable promise for tissue repair, albeit they encounter obstacles such as replicative senescence in laboratory conditions. In comparison, employing ADSCs within three-dimensional (3D) environments provides an innovative solution, replicating the natural extracellular matrix environment while offering a controlled and cost-effective in vitro platform. Moreover, the utilization of photobiomodulation (PBM) has emerged as a method to enhance ADSC differentiation and proliferation potential by instigating cellular stimulation and facilitating beneficial performance modifications. This literature review critically examines the shortcomings of current osteoporosis treatments and investigates the potential synergies between 3D cell culture and PBM in augmenting ADSC differentiation towards osteogenic lineages. The primary objective of this study is to assess the efficacy of combined 3D environments and PBM in enhancing ADSC performance for osteoporosis management. This research is notably distinguished by its thorough scrutiny of the existing literature, synthesis of recent advancements, identification of future research trajectories, and utilization of databases such as PubMed, Scopus, Web of Science, and Google Scholar for this literature review. Furthermore, the exploration of biomechanical and biophysical stimuli holds promise for refining treatment strategies. The future outlook suggests that integrating PBM with ADSCs housed within 3D environments holds considerable potential for advancing bone regeneration efforts. Importantly, this review aspires to catalyse further advancements in combined therapeutic strategies for osteoporosis regeneration.
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Affiliation(s)
| | | | - Heidi Abrahamse
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Johannesburg 2028, South Africa; (D.D.S.); (A.C.)
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11
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Balough JL, Moalli P. Regenerative Medicine in Gynecology. Obstet Gynecol 2024; 143:767-773. [PMID: 38663014 PMCID: PMC11216342 DOI: 10.1097/aog.0000000000005590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Accepted: 03/21/2024] [Indexed: 05/18/2024]
Abstract
The female reproductive tract undergoes dynamic changes across the life span. Congenital abnormalities, life events, and medical interventions can negatively affect the structure and function of reproductive tract organs, resulting in lifelong sequelae. The objective of regenerative gynecology is to discover and promote endogenous mechanisms by which a healthy tissue maintains overall tissue integrity after injury, after disease, or with age. In this review, we discuss some of the key state-of-the-art cell-based and scaffolding therapies that have been applied to regenerate gynecologic tissues and organs primarily in animal and tissue culture models. We further discuss the limitations of current technologies, problems of implementation and scalability, and future outlook of the field.
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Affiliation(s)
- Julia L. Balough
- Department of Obstetrics, Gynecology & Reproductive Science, University of Pittsburgh, Pittsburgh, PA
- Magee-Women’s Research Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Pamela Moalli
- Department of Obstetrics, Gynecology & Reproductive Science, University of Pittsburgh, Pittsburgh, PA
- Magee-Women’s Research Institute, University of Pittsburgh Medical Center, Pittsburgh, PA
- Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA
- The McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA
- Division of Urogynecology & Reconstructive Pelvic Surgery, University of Pittsburgh Medical Center Magee-Women’s Hospital, Pittsburgh, PA, USA
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12
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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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13
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Abouzid MR, Ali K, Kamel I, Esteghamati S, Saleh A, Ghanim M. The Safety and Efficacy of Human Umbilical Cord-Derived Mesenchymal Stem Cells in Patients With Heart Failure and Myocardial Infarction: A Meta-Analysis of Clinical Trials. Cureus 2023; 15:e49645. [PMID: 38033439 PMCID: PMC10686683 DOI: 10.7759/cureus.49645] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/29/2023] [Indexed: 12/02/2023] Open
Abstract
Evidence from preclinical and clinical studies suggests that human umbilical cord-derived mesenchymal stromal cells (HUC-MSCs) may be useful in treating heart failure and acute myocardial infarction (MI). However, the effects of stem cell therapy on patients with heart failure remain the subject of ongoing controversy, and the safety and effectiveness of HUC-MSCs therapy have not yet been proven. To date, there has been no systematic overview and meta-analysis of clinical studies using HUC-MSCs therapy for heart failure and MI. The purpose of this study is to assess the safety and efficacy of HUC-MSC therapy versus a placebo in patients with heart failure and MI. While preparing this systematic review and meta-analysis, we adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer literature search of PubMed was performed. We considered randomized controlled trials (RCTs) that reported data on the safety and efficacy of HUC-MSC transplantation in patients with heart failure and MI. Two investigators independently searched the literature, extracted data, and rated the quality of the included research. Pooled data were analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The primary outcome was ejection fraction (EF), whereas the secondary outcomes were readmission and mortality rates. Three RCTs (201 patients) were included in this meta-analysis. The overall effect did not favor either of the two groups in terms of risk of readmission (risk ratio = 0.5, 95% confidence interval (CI) = 0.22-1.15, p = 0.10) as well as mortality rate (risk ratio = 0.44, 95% CI = 0.14-1.44, p = 0.18). However, there was an improvement in EF in patients who received HUC-MSCs compared to placebo after 12 months of transplantation (mean difference (MD) = 3.21, 95% CI = 2.91-3.51, p < 0.00001). At the six-month follow-up period, there was no significant improvement in EF (MD = 1.30, 95% CI = -1.94-4.54), p = 0.43), indicating that the duration of follow-up can shape the response to therapy. Our findings indicate that HUC-MSC transplantation can improve EF but has no meaningful effect on readmission or mortality rates. Existing evidence is insufficient to confirm the efficacy of HUC-MSCs for broader therapeutic applications. Therefore, additional double-blind RCTs with larger sample sizes are required.
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Affiliation(s)
- Mohamed R Abouzid
- Internal Medicine, Baptist Hospitals of Southeast Texas, Beaumont, USA
| | - Karim Ali
- Internal Medicine, Hennepin Healthcare, Minneapolis, USA
| | - Ibrahim Kamel
- Internal Medicine, Steward Carney Hospital, Boston, USA
| | | | - Amr Saleh
- Faculty of Medicine, Mansoura University, Mansoura, EGY
| | - Mohammed Ghanim
- Internal Medicine, University Hospital Sharjah, Sharjah, ARE
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14
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Szukiewicz D. Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis. Int J Mol Sci 2023; 24:12195. [PMID: 37569571 PMCID: PMC10418522 DOI: 10.3390/ijms241512195] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/25/2023] [Accepted: 07/27/2023] [Indexed: 08/13/2023] Open
Abstract
Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10-15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis.
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Affiliation(s)
- Dariusz Szukiewicz
- Department of Biophysics, Physiology & Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, 02-004 Warsaw, Poland
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15
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Liu Y, Jiang L, Song W, Wang C, Yu S, Qiao J, Wang X, Jin C, Zhao D, Bai X, Zhang P, Wang S, Liu M. Ginsenosides on stem cells fate specification-a novel perspective. Front Cell Dev Biol 2023; 11:1190266. [PMID: 37476154 PMCID: PMC10354371 DOI: 10.3389/fcell.2023.1190266] [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: 03/20/2023] [Accepted: 06/22/2023] [Indexed: 07/22/2023] Open
Abstract
Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal.
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Affiliation(s)
- Ying Liu
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Leilei Jiang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Wenbo Song
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Chenxi Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Shiting Yu
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Juhui Qiao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Xinran Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Chenrong Jin
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Daqing Zhao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Xueyuan Bai
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Peiguang Zhang
- Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences Changchun, Changchun, Jilin, China
| | - Siming Wang
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
| | - Meichen Liu
- Northeast Asia Research Institute of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China
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16
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de Paula AP, de Lima JD, Bastos TSB, Czaikovski AP, dos Santos Luz RB, Yuasa BS, Smanioto CCS, Robert AW, Braga TT. Decellularized Extracellular Matrix: The Role of This Complex Biomaterial in Regeneration. ACS OMEGA 2023; 8:22256-22267. [PMID: 37396215 PMCID: PMC10308580 DOI: 10.1021/acsomega.2c06216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/12/2023] [Indexed: 07/04/2023]
Abstract
Organ transplantation is understood as a technique where an organ from a donor patient is transferred to a recipient patient. This practice gained strength in the 20th century and ensured advances in areas of knowledge such as immunology and tissue engineering. The main problems that comprise the practice of transplants involve the demand for viable organs and immunological aspects related to organ rejection. In this review, we address advances in tissue engineering for reversing the current challenges of transplants, focusing on the possible use of decellularized tissues in tissue engineering. We address the interaction of acellular tissues with immune cells, especially macrophages and stem cells, due to their potential use in regenerative medicine. Our goal is to exhibit data that demonstrate the use of decellularized tissues as alternative biomaterials that can be applied clinically as partial or complete organ substitutes.
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Affiliation(s)
| | - Jordana Dinorá de Lima
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
| | | | | | | | - Bruna Sadae Yuasa
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
| | | | - Anny Waloski Robert
- Stem
Cells Basic Biology Laboratory, Carlos Chagas
Institute − FIOCRUZ/PR, Curitiba, Parana 81350-010, Brazil
| | - Tárcio Teodoro Braga
- Department
of Pathology, Federal University of Parana, Curitiba, Parana 80060-000, Brazil
- Graduate
Program in Biosciences and Biotechnology, Institute Carlos Chagas, Fiocruz, Parana 81310-020, Brazil
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17
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Ahn HJ, Kim YJ, Myeong S, Huh G, Kim WS. Clinical Evaluation of Conditioned Media of Human Umbilical Cord Blood Mesenchymal Stem Cells for Improvement of Symptoms of Sensitive Skin: Prospective, Single Blinded, Split-face Study. Ann Dermatol 2023; 35:165-172. [PMID: 37290950 DOI: 10.5021/ad.21.287] [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: 07/22/2022] [Revised: 12/08/2022] [Accepted: 01/02/2023] [Indexed: 06/10/2023] Open
Abstract
BACKGROUND The exact definition of sensitive skin is not established yet. Since its high prevalence and significant influence on quality of life, it has become an important topic of research. Among various ingredients, conditioned media from umbilical cord blood-derived mesenchymal stem cells (UCB-MSC-CM) can be a promising source for the treatment of sensitive skin. OBJECTIVE We evaluated the efficacy and safety of UCB-MSC-CM on patients with sensitive skin. METHODS We designed a randomized, single blinded, prospective, split-face comparison study and enrolled thirty patients. All patients underwent nonablative fractional laser over the entire face before UCB-MSC-CM or normal saline was applied. Each facial area was randomly assigned to undergo treatment with either UCB-MSC-CM or normal saline. We performed three sessions at two-week intervals, and final results were assessed on six weeks after the last session. As an outcome measure, we evaluated a five-point global assessment scale, transepidermal water loss (TEWL), erythema index (EI) and Sensitive Scale-10. Twenty seven subjects were included in final analysis. RESULTS The treated side exhibited greater improvement compared to the untreated side based on a five-point global assessment scale. TEWL, EI of the treated side were significantly lower than those of the untreated side throughout study period. Sensitive Scale-10 was significantly improved after treatment. CONCLUSION The application of UCB-MSC-CM resulted in improved skin barrier function and reduced inflammatory responsiveness, which could provide beneficial effect on sensitive skin.
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Affiliation(s)
- Hee-Jin Ahn
- Derma Science R&D Center, Primoris International CO., LTD., Gwangmyeong, Korea
| | - Yoon-Jin Kim
- Derma Science R&D Center, Primoris International CO., LTD., Gwangmyeong, Korea
| | - Sujin Myeong
- Derma Science R&D Center, Primoris International CO., LTD., Gwangmyeong, Korea
| | - Gyoo Huh
- Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won-Serk Kim
- Department of Dermatology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
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18
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Cecerska-Heryć E, Pękała M, Serwin N, Gliźniewicz M, Grygorcewicz B, Michalczyk A, Heryć R, Budkowska M, Dołęgowska B. The Use of Stem Cells as a Potential Treatment Method for Selected Neurodegenerative Diseases: Review. Cell Mol Neurobiol 2023:10.1007/s10571-023-01344-6. [PMID: 37027074 DOI: 10.1007/s10571-023-01344-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 03/30/2023] [Indexed: 04/08/2023]
Abstract
Stem cells have been the subject of research for years due to their enormous therapeutic potential. Most neurological diseases such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are incurable or very difficult to treat. Therefore new therapies are sought in which autologous stem cells are used. They are often the patient's only hope for recovery or slowing down the progress of the disease symptoms. The most important conclusions arise after analyzing the literature on the use of stem cells in neurodegenerative diseases. The effectiveness of MSC cell therapy has been confirmed in ALS and HD therapy. MSC cells slow down ALS progression and show early promising signs of efficacy. In HD, they reduced huntingtin (Htt) aggregation and stimulation of endogenous neurogenesis. MS therapy with hematopoietic stem cells (HSCs) inducted significant recalibration of pro-inflammatory and immunoregulatory components of the immune system. iPSC cells allow for accurate PD modeling. They are patient-specific and therefore minimize the risk of immune rejection and, in long-term observation, did not form any tumors in the brain. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BM-MSC-EVs) and Human adipose-derived stromal/stem cells (hASCs) cells are widely used to treat AD. Due to the reduction of Aβ42 deposits and increasing the survival of neurons, they improve memory and learning abilities. Despite many animal models and clinical trial studies, cell therapy still needs to be refined to increase its effectiveness in the human body.
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Affiliation(s)
- Elżbieta Cecerska-Heryć
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland.
| | - Maja Pękała
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Natalia Serwin
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Marta Gliźniewicz
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Bartłomiej Grygorcewicz
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Anna Michalczyk
- Department of Psychiatry, Pomeranian Medical University of Szczecin, Broniewskiego 26, 71-460, Szczecin, Poland
| | - Rafał Heryć
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Marta Budkowska
- Department of Medical Analytics, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
| | - Barbara Dołęgowska
- Department of Laboratory Medicine, Pomeranian Medical University of Szczecin, PowstancowWielkopolskich 72, 70-111, Szczecin, Poland
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19
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Arshad M, Jalil F, Jaleel H, Ghafoor F. Bone marrow derived mesenchymal stem cells therapy for rheumatoid arthritis - a concise review of past ten years. Mol Biol Rep 2023; 50:4619-4629. [PMID: 36929285 DOI: 10.1007/s11033-023-08277-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 01/11/2023] [Indexed: 03/18/2023]
Abstract
Rheumatoid arthritis is an autoimmune disorder characterized by swelling in synovial joints and erosion of bones. The disease is normally treated with conventional drugs which provide only temporary relief to the symptoms. Over the past few years, mesenchymal stromal cells have become the center of attention for treating this disease due to their immuno-modulatory and anti-inflammatory characteristics. Various studies on treatment of rheumatoid arthritis by using these cells have shown positive outcomes in terms of reduction in the level of pain as well as improvement of the function and structure of joints. Mesenchymal stromal cells can be derived from multiple sources, however, the ones derived from bone marrow are considered most beneficial for treating several disorders including rheumatoid arthritis on account of being safer and more effective. This review summarizes all the preclinical and clinical studies which were conducted over the last ten years for therapy of rheumatoid arthritis utilizing these cells. The literature was reviewed using the terms "mesenchymal stem/stromal cells and rheumatoid arthritis'' and "bone marrow derived mesenchymal stromal cells and therapy of rheumatoid arthritis''. Data was extracted to enable the readers to have access to the most relevant information regarding advancement in therapeutic potential of these stromal cells. Additionally, this review will also help in fulfilling any gap in current knowledge of readers about the outcome of using these cells in animal models, cell line and in patients suffering from rheumatoid arthritis and other autoimmune disorders as well.
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Affiliation(s)
- Maria Arshad
- Department of Research & Innovation, Shalamar Institute of Health Sciences, Lahore, Pakistan.
| | - Fazal Jalil
- Department of Biotechnology, Abdul Wali Khan University, Mardan, Pakistan
| | - Hadiqa Jaleel
- Department of Research & Innovation, Shalamar Institute of Health Sciences, Lahore, Pakistan
| | - Farkhanda Ghafoor
- Department of Research & Innovation, Shalamar Institute of Health Sciences, Lahore, Pakistan
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20
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Szukiewicz D. Aberrant epigenetic regulation of estrogen and progesterone signaling at the level of endometrial/endometriotic tissue in the pathomechanism of endometriosis. VITAMINS AND HORMONES 2023; 122:193-235. [PMID: 36863794 DOI: 10.1016/bs.vh.2022.11.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Endometriosis is a term referring to a condition whereby the endometrial tissue is found outside the uterine cavity. This progressive and debilitating condition affects up to 15% of women of reproductive age. Due to the fact that endometriosis cells may express estrogen receptors (ERα, Erβ, GPER) and progesterone (P4) receptors (PR-A, PR-B), their growth, cyclic proliferation, and breakdown are similar to the processes occurring in the endometrium. The underlying etiology and pathogenesis of endometriosis are still not fully explained. The retrograde transport of viable menstrual endometrial cells with the retained ability to attach within the pelvic cavity, proliferate, differentiate and invade into the surrounding tissue explains the most widely accepted implantation theory. Endometrial stromal cells (EnSCs) with clonogenic potential constitute the most abundant population of cells within endometrium that resemble the properties of mesenchymal stem cells (MSCs). Accordingly, formation of the endometriotic foci in endometriosis may be due to a kind of EnSCs dysfunction. Increasing evidence indicates the underestimated role of epigenetic mechanisms in the pathogenesis of endometriosis. Hormone-mediated epigenetic modifications of the genome in EnSCs or even MSCs were attributed an important role in the etiopathogenesis of endometriosis. The roles of excess estrogen exposure and P4 resistance were also found to be crucial in the development of epigenetic homeostasis failure. Therefore, the aim of this review was to consolidate the current knowledge regarding the epigenetic background of EnSCs and MSCs and the changed properties due to estrogen/P4 imbalances in the context of the etiopathogenesis of endometriosis.
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Affiliation(s)
- Dariusz Szukiewicz
- Department of Biophysics, Physiology & Pathophysiology, Faculty of Health Sciences, Medical University of Warsaw, Warsaw, Poland.
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21
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Choi Y, Lee HK, Choi KC. Engineered adult stem cells: a promising tool for anti-cancer therapy. BMB Rep 2023; 56:71-77. [PMID: 36330711 PMCID: PMC9978368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/28/2022] [Accepted: 11/04/2022] [Indexed: 02/24/2023] Open
Abstract
Cancers are one of the most dreaded diseases in human history and have been targeted by numerous trials including surgery, chemotherapy, radiation therapy, and anti-cancer drugs. Adult stem cells (ASCs), which can regenerate tissues and repair damage, have emerged as leading therapeutic candidates due to their homing ability toward tumor foci. Stem cells can precisely target malicious tumors, thereby minimizing the toxicity of normal cells and unfavorable side effects. ASCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs), are powerful tools for delivering therapeutic agents to various primary and metastatic cancers. Engineered ASCs act as a bridge between the tumor sites and tumoricidal reagents, producing therapeutic substances such as exosomes, viruses, and anti-cancer proteins encoded by several suicide genes. This review focuses on various anti-cancer therapies implemented via ASCs and summarizes the recent treatment progress and shortcomings. [BMB Reports 2023; 56(2): 71-77].
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Affiliation(s)
- Youngdong Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Hong Kyu Lee
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Kyung-Chul Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
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22
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Choi Y, Lee HK, Choi KC. Engineered adult stem cells: a promising tool for anti-cancer therapy. BMB Rep 2023; 56:71-77. [PMID: 36330711 PMCID: PMC9978368 DOI: 10.5483/bmbrep.2022-0091] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Revised: 07/28/2022] [Accepted: 11/04/2022] [Indexed: 08/03/2023] Open
Abstract
Cancers are one of the most dreaded diseases in human history and have been targeted by numerous trials including surgery, chemotherapy, radiation therapy, and anti-cancer drugs. Adult stem cells (ASCs), which can regenerate tissues and repair damage, have emerged as leading therapeutic candidates due to their homing ability toward tumor foci. Stem cells can precisely target malicious tumors, thereby minimizing the toxicity of normal cells and unfavorable side effects. ASCs, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and hematopoietic stem cells (HSCs), are powerful tools for delivering therapeutic agents to various primary and metastatic cancers. Engineered ASCs act as a bridge between the tumor sites and tumoricidal reagents, producing therapeutic substances such as exosomes, viruses, and anti-cancer proteins encoded by several suicide genes. This review focuses on various anti-cancer therapies implemented via ASCs and summarizes the recent treatment progress and shortcomings. [BMB Reports 2023; 56(2): 71-77].
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Affiliation(s)
- Youngdong Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Hong Kyu Lee
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
| | - Kyung-Chul Choi
- Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea
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23
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Miotti G, Parodi PC, Ferrari A, Salati C, Zeppieri M. Stem Cells in Ophthalmology: From the Bench to the Bedside. HANDBOOK OF STEM CELL APPLICATIONS 2023:1-24. [DOI: 10.1007/978-981-99-0846-2_10-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 09/13/2023]
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24
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Miotti G, Parodi PC, Ferrari A, Salati C, Zeppieri M. Stem Cells in Ophthalmology: From the Bench to the Bedside. HANDBOOK OF STEM CELL APPLICATIONS 2023:1-24. [DOI: https:/doi.org/10.1007/978-981-99-0846-2_10-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 08/28/2023]
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25
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Estep BK, Kuhlmann CJ, Osuka S, Suryavanshi GW, Nagaoka-Kamata Y, Samuel CN, Blucas MT, Jepson CE, Goepfert PA, Kamata M. Skewed fate and hematopoiesis of CD34 + HSPCs in umbilical cord blood amid the COVID-19 pandemic. iScience 2022; 25:105544. [PMID: 36406860 PMCID: PMC9650991 DOI: 10.1016/j.isci.2022.105544] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 08/11/2022] [Accepted: 11/04/2022] [Indexed: 11/13/2022] Open
Abstract
Umbilical cord blood (UCB) is an irreplaceable source for hematopoietic stem progenitor cells (HSPCs). However, the effects of SARS-CoV-2 infection and COVID-19 vaccination on UCB phenotype, specifically the HSPCs therein, are currently unknown. We thus evaluated any effects of SARS-CoV-2 infection and/or COVID-19 vaccination from the mother on the fate and functionalities of HSPCs in the UCB. The numbers and frequencies of HSPCs in the UCB decreased significantly in donors with previous SARS-CoV-2 infection and more so with COVID-19 vaccination via the induction of apoptosis, likely mediated by IFN-γ-dependent pathways. Two independent hematopoiesis assays, a colony forming unit assay and a mouse humanization assay, revealed skewed hematopoiesis of HSPCs obtained from donors delivered from mothers with SARS-CoV-2 infection history. These results indicate that SARS-CoV-2 infection and COVID-19 vaccination impair the functionalities and survivability of HSPCs in the UCB, which would make unprecedented concerns on the future of HSPC-based therapies.
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Affiliation(s)
- Benjamin K. Estep
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
| | - Charles J. Kuhlmann
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
| | - Satoru Osuka
- Department of Neurosurgery, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA
| | - Gajendra W. Suryavanshi
- Division of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA
| | | | - Ciearria N. Samuel
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
| | - Madison T. Blucas
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
| | - Chloe E. Jepson
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
| | - Paul A. Goepfert
- Department of Medicine and Division of Infectious Diseases, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35205, USA
| | - Masakazu Kamata
- Department of Microbiology, University of Alabama at Birmingham, 845 19 Street South, Birmingham, AL 35205, USA
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26
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Lee S, Nam H, Joo KM, Lee SH. Advances in Neural Stem Cell Therapy for Spinal Cord Injury: Safety, Efficacy, and Future Perspectives. Neurospine 2022; 19:946-960. [PMID: 36351442 PMCID: PMC9816608 DOI: 10.14245/ns.2244658.329] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 10/19/2022] [Indexed: 11/11/2022] Open
Abstract
Spinal cord injury (SCI) is a devastating central nervous system injury that leads to severe disabilities in motor and sensory functions, causing significant deterioration in patients' quality of life. Owing to the complexity of SCI pathophysiology, there has been no effective treatment for reversing neural tissue damage and recovering neurological functions. Several novel therapies targeting different stages of pathophysiological mechanisms of SCI have been developed. Among these, treatments using stem cells have great potential for the regeneration of damaged neural tissues. In this review, we have summarized recent preclinical and clinical studies focusing on neural stem cells (NSCs). NSCs are multipotent cells with specific differentiation capabilities for neural lineage. Several preclinical studies have demonstrated the regenerative effects of transplanted NSCs in SCI animal models through both paracrine effects and direct neuronal differentiation, restoring synaptic connectivity and neural networks. Based on the positive results of several preclinical studies, phase I and II clinical trials using NSCs have been performed. Despite several hurdles and issues that need to be addressed in the clinical use of NSCs in patients with SCI, gradual progress in the technical development and therapeutic efficacy of NSCs treatments has enhanced the prospects for cell-based treatments in SCI.
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Affiliation(s)
- Sungjoon Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Nam
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea,Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea,Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Korea,Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea
| | - Kyeung-Min Joo
- Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea,Single Cell Network Research Center, Sungkyunkwan University School of Medicine, Suwon, Korea,Department of Anatomy & Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea,Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea,Corresponding Author Kyeung-Min Joo Department of Anatomy and Cell Biology, Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon 16419, Korea
| | - Sun-Ho Lee
- Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea,Stem Cell and Regenerative Medicine Institute, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea,Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea,Co-corresponding Author Sun-Ho Lee Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
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27
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Li G, Guan Y, Gu Y, Guo M, Ma W, Shao Q, Liu J, Ji X. Intermittent hypoxic conditioning restores neurological dysfunction of mice induced by long-term hypoxia. CNS Neurosci Ther 2022; 29:202-215. [PMID: 36401601 PMCID: PMC9804074 DOI: 10.1111/cns.13996] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 09/18/2022] [Accepted: 09/20/2022] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Central nervous system diseases are associated with hypoxia, which usually cause irreversible nerve damage, but the underlying mechanism is unclear and effective intervention strategies are lacking. This study was designed to explore the mechanism and treatment strategy of hypoxia-induced nerve injury. METHODS In this study, 13% O2 was used to treat mice for 0, 1, 3 7, and 14 days, Morris water maze and other animal behavior experiments were used to evaluate the neurological function of mice. TUNEL, BrdU, PCNA, DCX, and SOX2 staining were used to observe the apoptosis and proliferation of mouse neurons. RT-PCR and Iba1 staining were used to evaluate the release of inflammatory factors IL-1β, IL-6, and TNF-α and the activation of microglia. RESULTS Short-term hypoxia promotes neurogenesis, while long-term hypoxia inhibits neurogenesis. The changes in hypoxia-induced neurogenesis were positively correlated with neurological functions, but negatively correlated with apoptosis. Moreover, intermittent hypoxic conditioning restored long-term hypoxia-induced neurological dysfunction by promoting neural stem cell generation and inhibiting the release of inflammatory factors IL-1β, IL-6, and TNF-α and the activation of microglia. CONCLUSION Hypoxia promoted neurogenesis in a time-dependent manner, and intermittent hypoxic conditioning exerted a neuroprotective effect through promoting neural stem cell generation and suppressing inflammation induced by long-term hypoxia stress, which provided a novel concept to develop a treatment for hypoxia-related brain injury.
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Affiliation(s)
- Gaifen Li
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina,Department of Neurosurgery, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Yuying Guan
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina,Department of Neurosurgery, Xuanwu HospitalCapital Medical UniversityBeijingChina
| | - Yakun Gu
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina
| | - Mengyuan Guo
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina
| | - Wei Ma
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina
| | - Qianqian Shao
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina
| | - Jia Liu
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina
| | - Xunming Ji
- Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Beijing Advanced Innovation Center for Big Data‐based Precision MedicineCapital Medical UniversityBeijingChina,Department of Neurosurgery, Xuanwu HospitalCapital Medical UniversityBeijingChina
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28
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Wang Y, Xue Y, Guo HD. Intervention effects of traditional Chinese medicine on stem cell therapy of myocardial infarction. Front Pharmacol 2022; 13:1013740. [PMID: 36330092 PMCID: PMC9622800 DOI: 10.3389/fphar.2022.1013740] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2022] [Accepted: 10/03/2022] [Indexed: 11/13/2022] Open
Abstract
Cardiovascular diseases are the leading cause of global mortality, in which myocardial infarction accounts for 46% of total deaths. Although good progress has been achieved in medication and interventional techniques, a proven method to repair the damaged myocardium has not yet been determined. Stem cell therapy for damaged myocardial repair has evolved into a promising treatment for ischemic heart disease. However, low retention and poor survival of the injected stem cells are the major obstacles to achieving the intended therapeutic effects. Chinese botanical and other natural drug substances are a rich source of effective treatment for various diseases. As such, numerous studies have revealed the role of Chinese medicine in stem cell therapy for myocardial infarction treatment, including promoting proliferation, survival, migration, angiogenesis, and differentiation of stem cells. Here, we discuss the potential and limitations of stem cell therapy, as well as the regulatory mechanism of Chinese medicines underlying stem cell therapy. We focus on the evidence from pre-clinical trials and clinical practices, and based on traditional Chinese medicine theories, we further summarize the mechanisms of Chinese medicine treatment in stem cell therapy by the commonly used prescriptions. Despite the pre-clinical evidence showing that traditional Chinese medicine is helpful in stem cell therapy, there are still some limitations of traditional Chinese medicine therapy. We also systematically assess the detailed experimental design and reliability of included pharmacological research in our review. Strictly controlled animal models with multi-perspective pharmacokinetic profiles and high-grade clinical evidence with multi-disciplinary efforts are highly demanded in the future.
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Affiliation(s)
- Yu Wang
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yuezhen Xue
- Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
| | - Hai-dong Guo
- Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
- Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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29
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Stem cell membrane-coated abiotic nanomaterials for biomedical applications. J Control Release 2022; 351:174-197. [PMID: 36103910 DOI: 10.1016/j.jconrel.2022.09.012] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Revised: 09/06/2022] [Accepted: 09/07/2022] [Indexed: 12/15/2022]
Abstract
Nanoscale materials have been extensively employed for diagnostic and therapeutic purposes. However, the developed nanosystems still suffer from some limitations, namely the rapid elimination by the immune system, lack of targeting to specific cells, and insufficient biocompatibility. Therefore, novel strategies based upon a biomimetic approach have received attention to improving the pharmacokinetics and safety profile of nanosystems. One promising strategy is the application of a biomimetic coating consisting of cell membranes derived from different cell types onto nanoparticle cores. Stem cells have been investigated to develop targeted nanodevices owing to their excellent intrinsic tissue-specific homing features, protecting them from the immune system to reach the sites of inflammation. This targeting ability is conferred by a surface repertoire of stem cell-associated biomolecules. Such nanoscopical materials offer sustained circulation and boosted drug accumulation at target sites, augmenting therapeutic efficacy and safety. Additionally, the coating of nanoparticles with cell membranes acts as a camouflage mechanism to increase their circulation time. The current review explores the particular features of stem cell membrane coating as multifunctional biomimetic surface functionalization agents to camouflage nanoparticle cores. Biomedical applications of engineered stem cell membrane-coated nanoparticles, challenges in clinical translation, and their future prospects are addressed.
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30
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Stolzenbach V, Woods DC, Tilly JL. Non-neutral clonal selection and its potential role in mammalian germline stem cell dysfunction with advancing age. Front Cell Dev Biol 2022; 10:942652. [PMID: 36081905 PMCID: PMC9445274 DOI: 10.3389/fcell.2022.942652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 07/20/2022] [Indexed: 11/13/2022] Open
Abstract
The concept of natural selection, or "survival of the fittest", refers to an evolutionary process in nature whereby traits emerge in individuals of a population through random gene alterations that enable those individuals to better adapt to changing environmental conditions. This genetic variance allows certain members of the population to gain an advantage over others in the same population to survive and reproduce in greater numbers under new environmental pressures, with the perpetuation of those advantageous traits in future progeny. Here we present that the behavior of adult stem cells in a tissue over time can, in many respects, be viewed in the same manner as evolution, with each stem cell clone being representative of an individual within a population. As stem cells divide or are subjected to cumulative oxidative damage over the lifespan of the organism, random genetic alterations are introduced into each clone that create variance in the population. These changes may occur in parallel to, or in response to, aging-associated changes in microenvironmental cues perceived by the stem cell population. While many of these alterations will be neutral or silent in terms of affecting cell function, a small fraction of these changes will enable certain clones to respond differently to shifts in microenvironmental conditions that arise with advancing age. In some cases, the same advantageous genetic changes that support survival and expansion of certain clones over others in the population (viz. non-neutral competition) could be detrimental to the downstream function of the differentiated stem cell descendants. In the context of the germline, such a situation would be devastating to successful propagation of the species across generations. However, even within a single generation, the “evolution” of stem cell lineages in the body over time can manifest into aging-related organ dysfunction and failure, as well as lead to chronic inflammation, hyperplasia, and cancer. Increased research efforts to evaluate stem cells within a population as individual entities will improve our understanding of how organisms age and how certain diseases develop, which in turn may open new opportunities for clinical detection and management of diverse pathologies.
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31
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Dental Pulp-Derived Stem Cells Reduce Inflammation, Accelerate Wound Healing and Mediate M2 Polarization of Myeloid Cells. Biomedicines 2022; 10:biomedicines10081999. [PMID: 36009546 PMCID: PMC9624276 DOI: 10.3390/biomedicines10081999] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 08/11/2022] [Accepted: 08/15/2022] [Indexed: 01/09/2023] Open
Abstract
This work aimed to validate the potential use of dental pulp-derived stem cells (DPSCs) for the treatment of inflammation by defining their mechanisms of action. We planned to investigate whether priming of DPSC with proinflammatory molecules had any impact on their behavior and function. In the first step of our validation in vitro, we showed that priming of DPSCs with the bioactive agents LPS, TNF-α, or IFN-γ altered DPSCs’ immunologic properties by increasing their expression levels of IL-10, HGF, IDO, and IL-4 and by decreasing their mitochondrial functions. Moreover, DPSCs induced accelerated wound healing irrespective of priming, as determined by using a gut epithelial cell line in a scratch wound assay. Wound healing of gut epithelial cells was mediated by regulating the expressions of AKT, NF-κB, and ERK1/2 proteins compared to the control epithelial cells. In addition, primed DPSCs altered monocyte polarization toward an immuno-suppressive phenotype (M2), where monocytes expressed higher levels of IL-4R, IL-6, Arg1, and YM-1 compared to monocytes cultured with control DPSCs. In silico analysis revealed that this was accomplished in part by the interaction between kynurenine and PPARγ, which regulated the expression of M2 differentiation-related genes. Collectively, these data provided evidence that the DPSCs reduced inflammation, induced M2 polarization of myeloid cells, and healed damaged gut epithelial cells through inactivation of inflammation and modulating constitutively active signaling pathways.
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32
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Krishnan A, Muthusamy S, Fernandez FB, Kasoju N. Mesenchymal Stem Cell-Derived Extracellular Vesicles in the Management of COVID19-Associated Lung Injury: A Review on Publications, Clinical Trials and Patent Landscape. Tissue Eng Regen Med 2022; 19:659-673. [PMID: 35384633 PMCID: PMC8985390 DOI: 10.1007/s13770-022-00441-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 01/27/2022] [Accepted: 02/02/2022] [Indexed: 02/07/2023] Open
Abstract
The unprecedented COVID-19 pandemic situation forced the scientific community to explore all the possibilities from various fields, and so far we have seen a lot of surprises, eureka moments and disappointments. One of the approaches from the cellular therapists was exploiting the immunomodulatory and regenerative potential of mesenchymal stromal cells (MSCs), more so of MSC-derived extracellular vesicles (EVs)-particularly exosomes, in order to alleviate the cytokine storm and regenerate the damaged lung tissues. Unlike MSCs, the EVs are easier to store, deliver, and are previously shown to be as effective as MSCs, yet less immunogenic. These features attracted the attention of many and thus led to a tremendous increase in publications, clinical trials and patent applications. This review presents the current landscape of the field and highlights some interesting findings on MSC-derived EVs in the context of COVID-19, including in silico, in vitro, in vivo and case reports. The data strongly suggests the potential of MSC-derived EVs as a therapeutic regime for the management of acute lung injury and associated complications in COVID-19 and beyond.
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Affiliation(s)
- Anand Krishnan
- Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Thiruvananthapuram, 695012, Kerala, India
| | - Senthilkumar Muthusamy
- Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Thiruvananthapuram, 695012, Kerala, India
| | - Francis B Fernandez
- Department of Biomaterial Science and Technology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Thiruvananthapuram, 695012, Kerala, India
| | - Naresh Kasoju
- Department of Applied Biology, Biomedical Technology Wing, Sree Chitra Tirunal Institute for Medical Science and Technology, Thiruvananthapuram, 695012, Kerala, India.
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33
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Mosaddad SA, Rasoolzade B, Namanloo RA, Azarpira N, Dortaj H. Stem cells and common biomaterials in dentistry: a review study. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2022; 33:55. [PMID: 35716227 PMCID: PMC9206624 DOI: 10.1007/s10856-022-06676-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/16/2022] [Indexed: 05/16/2023]
Abstract
Stem cells exist as normal cells in embryonic and adult tissues. In recent years, scientists have spared efforts to determine the role of stem cells in treating many diseases. Stem cells can self-regenerate and transform into some somatic cells. They would also have a special position in the future in various clinical fields, drug discovery, and other scientific research. Accordingly, the detection of safe and low-cost methods to obtain such cells is one of the main objectives of research. Jaw, face, and mouth tissues are the rich sources of stem cells, which more accessible than other stem cells, so stem cell and tissue engineering treatments in dentistry have received much clinical attention in recent years. This review study examines three essential elements of tissue engineering in dentistry and clinical practice, including stem cells derived from the intra- and extra-oral sources, growth factors, and scaffolds.
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Affiliation(s)
- Seyed Ali Mosaddad
- Student Research Committee, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Boshra Rasoolzade
- Student Research Committee, Department of Pediatric Dentistry, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hengameh Dortaj
- Department of Tissue Engineering, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
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34
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Ou M, Li Q, Ling X, Yao J, Mo X. Cocktail Formula and Application Prospects for Oral and Maxillofacial Organoids. Tissue Eng Regen Med 2022; 19:913-925. [PMID: 35612711 DOI: 10.1007/s13770-022-00455-3] [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: 01/02/2022] [Revised: 03/18/2022] [Accepted: 03/22/2022] [Indexed: 11/24/2022] Open
Abstract
Oral and maxillofacial organoids (OMOs), tiny tissues and organs derived from stem cells cultured through 3-d cell culture models, can fully summarize the cell tissue structure, physiological functions and biological characteristics of the source tissues in the body. OMOs are applied in areas such as disease modelling, developmental and regenerative medicine, drug screening, personalized treatment, etc. Although the construction of organoids in various parts of the oral and maxillofacial (OM) region has achieved considerable success, the existing cocktail formulae (construction strategies) are not widely applicable for tissues of various sources due to factors including the heterogeneity of the source tissues and the dependence on laboratory technology. Most of their formulae are based on growth factor niches containing expensive recombinant proteins with their efficiency remaining to be improved. In view of this, the cocktail formulae of various parts of the OM organs are reviewed with further discussion of the application and prospects for those OMOs to find some affordable cocktail formula with strong operability and high repeatability for various maxillofacial organs. The results may help improve the efficiency of organoid construction in the laboratory and accelerate the pace of the clinical use of organoid technology.
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Affiliation(s)
- Mingyu Ou
- Youjiang Medical University for Nationalities, No. 98 Countryside Road, BaiseGuangxi, 533000, China.,Department of Stomatology, China Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Second Zhongshan Road, BaiseGuangxi, 533000, China
| | - Qing Li
- Youjiang Medical University for Nationalities, No. 98 Countryside Road, BaiseGuangxi, 533000, China.,Department of Stomatology, China Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Second Zhongshan Road, BaiseGuangxi, 533000, China
| | - Xiaofang Ling
- Youjiang Medical University for Nationalities, No. 98 Countryside Road, BaiseGuangxi, 533000, China.,Department of Stomatology, China Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Second Zhongshan Road, BaiseGuangxi, 533000, China
| | - Jinguang Yao
- Youjiang Medical University for Nationalities, No. 98 Countryside Road, BaiseGuangxi, 533000, China. .,Department of Stomatology, China Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Second Zhongshan Road, BaiseGuangxi, 533000, China.
| | - Xiaoqiang Mo
- Youjiang Medical University for Nationalities, No. 98 Countryside Road, BaiseGuangxi, 533000, China.
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35
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Du S, Li Y, Geng Z, Zhang Q, Buhler LH, Gonelle-Gispert C, Wang Y. Engineering Islets From Stem Cells: The Optimal Solution for the Treatment of Diabetes? Front Immunol 2022; 13:869514. [PMID: 35572568 PMCID: PMC9092457 DOI: 10.3389/fimmu.2022.869514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Accepted: 03/25/2022] [Indexed: 11/13/2022] Open
Abstract
Diabetes is a metabolic disease characterized by insulin deficiency. Bioengineering of stem cells with the aim to restore insulin production and glucose regulation has the potential to cure diabetic patients. In this review, we focus on the recent developments for bioengineering of induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), embryonic stem cells (ESCs), and pancreatic progenitor cells in view of generating insulin producing and glucose regulating cells for β-cell replacement therapies. Recent clinical trials using islet cells derived from stem cells have been initiated for the transplantation into diabetic patients, with crucial bottlenecks of tumorigenesis, post-transplant survival, genetic instability, and immunogenicity that should be further optimized. As a new approach given high expectations, bioengineered islets from stem cells occupies considerable potential for the future clinical application and addressing the treatment dilemma of diabetes.
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Affiliation(s)
- Suya Du
- Department of Clinical Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yanjiao Li
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhen Geng
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Center of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.,Institute of Organ Transplantation, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
| | - Qi Zhang
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Leo H Buhler
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Center of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.,Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
| | | | - Yi Wang
- Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province, Center of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, China.,Institute of Organ Transplantation, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.,Chinese Academy of Sciences, Sichuan Translational Medicine Research Hospital, Chengdu, China
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Guindolet D, Woodward AM, Gabison EE, Argüeso P. Glycogene Expression Profile of Human Limbal Epithelial Cells with Distinct Clonogenic Potential. Cells 2022; 11:cells11091575. [PMID: 35563881 PMCID: PMC9102009 DOI: 10.3390/cells11091575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/05/2022] [Accepted: 05/06/2022] [Indexed: 12/13/2022] Open
Abstract
Glycans function as valuable markers of stem cells but also regulate the ability of these cells to self-renew and differentiate. Approximately 2% of the human genome encodes for proteins that are involved in the biosynthesis and recognition of glycans. In the present study, we evaluated the expression of a small subset of glycogenes in human limbal epithelial cells with distinct clonogenic potential. Individual clones were classified as abortive or clonogenic, based on the fraction of the terminal colonies produced; clones leading exclusively to terminal colonies were referred to as abortive while those with half or fewer terminal colonies were referred to as clonogenic. An analysis of glycogene expression in clonogenic cultures revealed a high content of transcripts regulating the galactose and mannose metabolic pathways. Abortive clones were characterized by increased levels of GCNT4 and FUCA2, genes that are responsible for the branching of mucin-type O-glycans and the hydrolysis of fucose residues on N-glycans, respectively. The expansion of primary cultures of human limbal epithelial cells for 10 days resulted in stratification and a concomitant increase in MUC16, GCNT4 and FUCA2 expression. These data indicate that the clonogenic potential of human limbal epithelial cells is associated with specific glycosylation pathways. Mucin-type O-glycan branching and increased fucose metabolism are linked to limbal epithelial cell differentiation.
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Affiliation(s)
- Damien Guindolet
- Schepens Eye Research Institute of Mass. Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA; (D.G.); (A.M.W.)
- Hôpital Fondation A. de Rothschild, Department of Ophthalmology, 25 rue Manin, 75019 Paris, France
| | - Ashley M. Woodward
- Schepens Eye Research Institute of Mass. Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA; (D.G.); (A.M.W.)
| | - Eric E. Gabison
- Hôpital Fondation A. de Rothschild, Department of Ophthalmology, 25 rue Manin, 75019 Paris, France
- Correspondence: (E.E.G.); (P.A.)
| | - Pablo Argüeso
- Schepens Eye Research Institute of Mass. Eye and Ear, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA; (D.G.); (A.M.W.)
- Correspondence: (E.E.G.); (P.A.)
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Wei B, Zeng M, Yang J, Li S, Zhang J, Ding N, Jiang Z. N6-Methyladenosine RNA Modification: A Potential Regulator of Stem Cell Proliferation and Differentiation. Front Cell Dev Biol 2022; 10:835205. [PMID: 35445023 PMCID: PMC9013802 DOI: 10.3389/fcell.2022.835205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/09/2022] [Indexed: 11/30/2022] Open
Abstract
Stem cell transplantation (SCT) holds great promise for overcoming diseases by regenerating damaged cells, tissues and organs. The potential for self-renewal and differentiation is the key to SCT. RNA methylation, a dynamic and reversible epigenetic modification, is able to regulate the ability of stem cells to differentiate and regenerate. N6-methyladenosine (m6A) is the richest form of RNA methylation in eukaryotes and is regulated by three classes of proteins: methyltransferase complexes, demethylase complexes and m6A binding proteins. Through the coordination of these proteins, RNA methylation precisely modulates the expression of important target genes by affecting mRNA stability, translation, selective splicing, processing and microRNA maturation. In this review, we summarize the most recent findings on the regulation of m6A modification in embryonic stem cells, induced pluripotent stem cells and adult stem cells, hoping to provide new insights into improving SCT technology.
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Affiliation(s)
- Bo Wei
- Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, China
- Key Laboratory for Arteriosclerology of Hunan Province, Human International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Institute of Cardiovascular Disease, Hengyang Medical College, University of South China, Hengyang, China
| | - Meiyu Zeng
- Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, China
| | - Jing Yang
- Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, China
| | - Shuainan Li
- Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, China
| | - Jiantao Zhang
- Institution of Pathogenic Biology, Hengyang Medical School, University of South China, Hengyang, China
| | - Nan Ding
- Institution of Pathogenic Biology, Hengyang Medical School, University of South China, Hengyang, China
- *Correspondence: Nan Ding, ; Zhisheng Jiang,
| | - Zhisheng Jiang
- Key Laboratory for Arteriosclerology of Hunan Province, Human International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Institute of Cardiovascular Disease, Hengyang Medical College, University of South China, Hengyang, China
- *Correspondence: Nan Ding, ; Zhisheng Jiang,
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Liu Y, Schwam J, Chen Q. Senescence-Associated Cell Transition and Interaction (SACTAI): A Proposed Mechanism for Tissue Aging, Repair, and Degeneration. Cells 2022; 11:1089. [PMID: 35406653 PMCID: PMC8997723 DOI: 10.3390/cells11071089] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/21/2022] [Accepted: 03/22/2022] [Indexed: 02/01/2023] Open
Abstract
Aging is a broad process that occurs as a time-dependent functional decline and tissue degeneration in living organisms. On a smaller scale, aging also exists within organs, tissues, and cells. As the smallest functional unit in living organisms, cells "age" by reaching senescence where proliferation stops. Such cellular senescence is achieved through replicative stress, telomere erosion and stem cell exhaustion. It has been shown that cellular senescence is key to tissue degradation and cell death in aging-related diseases (ARD). However, senescent cells constitute only a small percentage of total cells in the body, and they are resistant to death during aging. This suggests that ARD may involve interaction of senescent cells with non-senescent cells, resulting in senescence-triggered death of non-senescent somatic cells and tissue degeneration in aging organs. Here, based on recent research evidence from our laboratory and others, we propose a mechanism-Senescence-Associated Cell Transition and Interaction (SACTAI)-to explain how cell heterogeneity arises during aging and how the interaction between somatic cells and senescent cells, some of which are derived from aging somatic cells, results in cell death and tissue degeneration.
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Affiliation(s)
| | | | - Qian Chen
- Laboratory of Molecular Biology and Nanomedicine, Department of Orthopaedics, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, RI 02903, USA; (Y.L.); (J.S.)
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Liu L, Liu X, Liu M, Jihu Y, Xie D, Yan H. Mechanical signals induces reprogramming of mature adipocytes through the YAP/TAZ-binding motif. Exp Cell Res 2022; 415:113109. [DOI: 10.1016/j.yexcr.2022.113109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Revised: 02/18/2022] [Accepted: 03/18/2022] [Indexed: 12/29/2022]
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Gasanova SY. [Cell therapy for destructive pancreatitis]. Khirurgiia (Mosk) 2022:50-55. [PMID: 36073583 DOI: 10.17116/hirurgia202209150] [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: 06/15/2023]
Abstract
OBJECTIVE To evaluate therapeutic efficacy of mesenchymal stem cells in patients with severe acute pancreatitis. MATERIAL AND METHODS There were 60 patients with severe acute pancreatitis randomized into 2 groups: the first group (n=30) - endoscopic surgical treatment, mean age 44.7±2.93 years (18 (60.0%) males and 12 (40.0%) females); the second group (n=30) - complex therapy (standard treatment + cell therapy), mean age 50.8±3.8 years (16 (53.3%) men and 14 (46.7%) women). Taxation of endogenous intoxication, immunity state and regional microcirculation were assessed. Genetic analysis of eNOS (C774T) gene polymorphism was also carried out. RESULTS Early period of acute severe pancreatitis is accompanied by significant disorders of homeostasis (endogenous intoxication, immune imbalance, severe disorders of regional microcirculation). Genetic analysis showed that polymorphic genotype (T774T) of the endothelial NO synthase gene in a larger percentage (66.7-71.6%, p=0.001) occur in patients with severe acute pancreatitis and more severe homeostatic disorders (p<0.05). Inclusion of mesenchymal stem cells into standard therapy in early phase of acute severe pancreatitis makes it possible to purposefully and relatively quickly exert its effect on abnormal processes of homeostasis, inhibiting toxemic phenomenon, restoring immune response, and improving microcirculation. A particularly positive therapeutic effect of the drug is observed in patients with the eNOS gene mutation (T774T). CONCLUSION Mesenchymal stem cell drugs are advisable in early period of acute pancreatitis, mainly in patients with severe forms of disease.
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Affiliation(s)
- S Yu Gasanova
- Aliyev Azerbaijan State Institute for Advanced Training of Physicians, Azerbaijan, Baku
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Abstract
A simple, universal and fundamental definition of adult stem cell communities is proposed. Key principles of cell lineage methods for defining adult stem cell numbers, locations and behaviors are critically evaluated, emphasizing the imperatives of capturing the full spectrum of individual stem cell behaviors, examining a variety of experimental time periods and avoiding unwarranted assumptions. The focus is first on defining fundamentals and then addresses stem cell heterogeneity, potential hierarchies and how individual cells serve the function of a stem cell community.
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Zhang Q, Wan XX, Hu XM, Zhao WJ, Ban XX, Huang YX, Yan WT, Xiong K. Targeting Programmed Cell Death to Improve Stem Cell Therapy: Implications for Treating Diabetes and Diabetes-Related Diseases. Front Cell Dev Biol 2021; 9:809656. [PMID: 34977045 PMCID: PMC8717932 DOI: 10.3389/fcell.2021.809656] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 12/06/2021] [Indexed: 12/14/2022] Open
Abstract
Stem cell therapies have shown promising therapeutic effects in restoring damaged tissue and promoting functional repair in a wide range of human diseases. Generations of insulin-producing cells and pancreatic progenitors from stem cells are potential therapeutic methods for treating diabetes and diabetes-related diseases. However, accumulated evidence has demonstrated that multiple types of programmed cell death (PCD) existed in stem cells post-transplantation and compromise their therapeutic efficiency, including apoptosis, autophagy, necroptosis, pyroptosis, and ferroptosis. Understanding the molecular mechanisms in PCD during stem cell transplantation and targeting cell death signaling pathways are vital to successful stem cell therapies. In this review, we highlight the research advances in PCD mechanisms that guide the development of multiple strategies to prevent the loss of stem cells and discuss promising implications for improving stem cell therapy in diabetes and diabetes-related diseases.
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Affiliation(s)
- Qi Zhang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Xin-xing Wan
- Department of Endocrinology, Third Xiangya Hospital, Central South University, Changsha, China
| | - Xi-min Hu
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wen-juan Zhao
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Xiao-xia Ban
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Yan-xia Huang
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Wei-tao Yan
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
| | - Kun Xiong
- Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China
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El-Kadiry AEH, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne) 2021; 8:756029. [PMID: 34881261 PMCID: PMC8645794 DOI: 10.3389/fmed.2021.756029] [Citation(s) in RCA: 112] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 11/01/2021] [Indexed: 12/12/2022] Open
Abstract
Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review article, we delineate the vast types of cell therapy, including stem cell-based and non-stem cell-based cell therapies, and create the first-in-literature compilation of the different "multicellular" therapies used in clinical settings. Besides providing the nuts and bolts of FDA policies regulating their use, we discuss the benefits of cell therapies reported in 3 therapeutic areas-regenerative medicine, immune diseases, and cancer. Finally, we contemplate the recent attention shift toward combined therapy approaches, highlighting the factors that render multicellular therapies a more attractive option than their unicellular counterparts.
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Affiliation(s)
- Abed El-Hakim El-Kadiry
- Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, Research Center, Montreal, QC, Canada
- Department of Biomedical Sciences, Université de Montréal, Montreal, QC, Canada
| | - Moutih Rafei
- Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC, Canada
- Molecular Biology Program, Université de Montréal, Montreal, QC, Canada
- Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada
| | - Riam Shammaa
- Canadian Centre for Regenerative Therapy, Toronto, ON, Canada
- Department of Family and Community Medicine, University of Toronto, Toronto, ON, Canada
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Identification and characterization of murine adipose tissue-derived somatic stem cells of Shenque (CV8) acupoint. Chin Med J (Engl) 2021; 134:2730-2737. [PMID: 34732664 PMCID: PMC8631409 DOI: 10.1097/cm9.0000000000001850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Background: Shenque (CV8) acupoint is located on the navel and has been therapeutically used for more than 2000 years in Traditional Chinese Medicine (TCM). However, clinical research on the underlying therapeutic molecular mechanisms of the CV8 acupoint lags far behind. This study aimed to study the mechanisms of umbilical acupoint therapy by using stem cells. Methods: The morphological characteristics of CV8 acupoint were detected under a stereomicroscope using hematoxylin and eosin (H&E) staining. Oil Red, Masson, and immunohistochemical staining on multi-layered slices were used to identify the type of cells at the CV8 acupoint. Cell proliferation was measured by a cell counting kit-8 (CCK-8) method. Flow cytometry and immunohistochemistry were used for cell identification. Induced differentiation was used to compare the differentiation of cells derived from CV8 acupoint and non-acupoint somatic stem cells into other cell types, such as osteogenic, adipogenic, and neural stem cell-like cells. Results: Morphological observations showed that adipose tissues at the linea alba of the CV8 acupoint in mice had a mass-like distribution. Immunohistochemical staining confirmed the distribution of stem cell antigen-1 (Sca-1) positive cells in the multi-layered slices of CV8 acupoint tissues. Cells isolated from adipose tissues at the CV8 acupoint exhibited high expression of Sca-1 and CD44 and low expression of CD31 and CD34, and these cells possessed osteogenic, adipogenic, and neurogenic stem cell-like cell differentiation ability. The cell proliferation (day 4: 0.5138 ± 0.0111 vs. 0.4107 ± 0.0180, t = 8.447, P = 0.0011; day 5: 0.6890 ± 0.0070 vs. 0.5520 ± 0.0118, t = 17.310, P < 0.0001; day 6: 0.7320 ± 0.0090 vs. 0.6157 ± 0.0123, t = 13.190, P = 0.0002; and day 7: 0.7550 ± 0.0050 vs. 0.6313 ± 0.0051, t = 42.560, P < 0.0001), adipogenic ([9.224 ± 0.345]% vs. [3.933 ± 1.800]%, t = 5.000, P = 0.0075), and neurogenic stem cell-like cell differentiation (diameter < 50 μm: 7.2000 ± 1.3040 vs. 2.6000 ± 0.5477, t = 7.273, P < 0.0001; diameter 50–100 μm: 2.6000 ± 0.5477 vs. 1.0000 ± 0.7071, t = 4.000, P = 0.0039; and diameter >100 μm: 2.6000 ± 0.5477 vs. 0.8000 ± 0.8367, t = 4.025, P = 0.0038) were significantly enhanced in somatic stem cells derived from the CV8 acupoint compared to somatic stem cells from the groin non-acupoint. However, cells possessed significantly weaker osteogenicity ([2.697 ± 0.627]% vs. [7.254 ± 0.958]%, t = 6.893, P = 0.0023) in the CV8 acupoint group. Conclusions: Our study showed that CV8 acupoint was rich with adipose tissues that contained abundant somatic stem cells. The biological examination of somatic stem cells derived from the CV8 acupoint provided novel insights for future research on the mechanisms of umbilical therapy.
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Understanding Drivers of Ocular Fibrosis: Current and Future Therapeutic Perspectives. Int J Mol Sci 2021; 22:ijms222111748. [PMID: 34769176 PMCID: PMC8584003 DOI: 10.3390/ijms222111748] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 10/22/2021] [Accepted: 10/27/2021] [Indexed: 01/10/2023] Open
Abstract
Ocular fibrosis leads to severe visual impairment and blindness worldwide, being a major area of unmet need in ophthalmology and medicine. To date, the only available treatments are antimetabolite drugs that have significant potentially blinding side effects, such as tissue damage and infection. There is thus an urgent need to identify novel targets to prevent/treat scarring and postsurgical fibrosis in the eye. In this review, the latest progress in biological mechanisms underlying ocular fibrosis are discussed. We also summarize the current knowledge on preclinical studies based on viral and non-viral gene therapy, as well as chemical inhibitors, for targeting TGFβ or downstream effectors in fibrotic disorders of the eye. Moreover, the role of angiogenetic and biomechanical factors in ocular fibrosis is discussed, focusing on related preclinical treatment approaches. Moreover, we describe available evidence on clinical studies investigating the use of therapies targeting TGFβ-dependent pathways, angiogenetic factors, and biomechanical factors, alone or in combination with other strategies, in ocular tissue fibrosis. Finally, the recent progress in cell-based therapies for treating fibrotic eye disorders is discussed. The increasing knowledge of these disorders in the eye and the promising results from testing of novel targeted therapies could offer viable perspectives for translation into clinical use.
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Alfaro-García JP, Granados-Alzate MC, Vicente-Manzanares M, Gallego-Gómez JC. An Integrated View of Virus-Triggered Cellular Plasticity Using Boolean Networks. Cells 2021; 10:cells10112863. [PMID: 34831086 PMCID: PMC8616224 DOI: 10.3390/cells10112863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 10/18/2021] [Accepted: 10/22/2021] [Indexed: 11/16/2022] Open
Abstract
Virus-related mortality and morbidity are due to cell/tissue damage caused by replicative pressure and resource exhaustion, e.g., HBV or HIV; exaggerated immune responses, e.g., SARS-CoV-2; and cancer, e.g., EBV or HPV. In this context, oncogenic and other types of viruses drive genetic and epigenetic changes that expand the tumorigenic program, including modifications to the ability of cancer cells to migrate. The best-characterized group of changes is collectively known as the epithelial–mesenchymal transition, or EMT. This is a complex phenomenon classically described using biochemistry, cell biology and genetics. However, these methods require enormous, often slow, efforts to identify and validate novel therapeutic targets. Systems biology can complement and accelerate discoveries in this field. One example of such an approach is Boolean networks, which make complex biological problems tractable by modeling data (“nodes”) connected by logical operators. Here, we focus on virus-induced cellular plasticity and cell reprogramming in mammals, and how Boolean networks could provide novel insights into the ability of some viruses to trigger uncontrolled cell proliferation and EMT, two key hallmarks of cancer.
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Affiliation(s)
- Jenny Paola Alfaro-García
- Molecular and Translation Medicine Group, Faculty of Medicine, University of Antioquia, Medellin 050010, Colombia; (J.P.A.-G.); (M.C.G.-A.)
| | - María Camila Granados-Alzate
- Molecular and Translation Medicine Group, Faculty of Medicine, University of Antioquia, Medellin 050010, Colombia; (J.P.A.-G.); (M.C.G.-A.)
| | - Miguel Vicente-Manzanares
- Molecular Mechanisms Program, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, 37007 Salamanca, Spain
- Correspondence: (M.V.-M.); (J.C.G.-G.)
| | - Juan Carlos Gallego-Gómez
- Molecular and Translation Medicine Group, Faculty of Medicine, University of Antioquia, Medellin 050010, Colombia; (J.P.A.-G.); (M.C.G.-A.)
- Correspondence: (M.V.-M.); (J.C.G.-G.)
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Engrafted stem cell therapy for Alzheimer's disease: A promising treatment strategy with clinical outcome. J Control Release 2021; 338:837-857. [PMID: 34509587 DOI: 10.1016/j.jconrel.2021.09.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 09/06/2021] [Accepted: 09/07/2021] [Indexed: 12/27/2022]
Abstract
To date, although the microscopic alterations present in Alzheimer's disease (AD) have been well known for over a century only a handful of symptomatic treatments have been developed which are a far cry from a full cure providing volatile benefits. In this context, the intervention of stem cell therapy (SCT) has been proposed as an auxiliary treatment for AD as suggested by the rising number of pre-clinical studies that stem cell engraftment could provide an exciting future treatment regimen against neurodegeneration. Although, most of the primary enthusiasm about this approach was based on replacing deteriorating neurons, the latest studies have implied that the positive modulations fostered by stem cells are fuelled by bystander effects. Present review provides a detailed update on stem cell therapy for AD along with meticulous discussion regarding challenges in developing different stem cells from an aspect of experiment to clinical research and their potential in the milieu of AD hallmarks. Specifically, we focus and provide in depth view on recent advancements in the discipline of SCT aiming to repopulate or regenerate the degenerating neuronal circuitry in AD using stem-cell-on-a-chip and 3D bioprinting techniques. The focus is specifically on the successful restoration of cognitive functions upon engraftment of stem cells on in vivo models for the benefit of the current researchers and their understanding about the status of SCT in AD and finally summarizing on what future holds for SCT in the treatment of AD.
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48
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Berlet R, Anthony S, Brooks B, Wang ZJ, Sadanandan N, Shear A, Cozene B, Gonzales-Portillo B, Parsons B, Salazar FE, Lezama Toledo AR, Monroy GR, Gonzales-Portillo JV, Borlongan CV. Combination of Stem Cells and Rehabilitation Therapies for Ischemic Stroke. Biomolecules 2021; 11:1316. [PMID: 34572529 PMCID: PMC8468342 DOI: 10.3390/biom11091316] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 08/31/2021] [Accepted: 09/01/2021] [Indexed: 12/14/2022] Open
Abstract
Stem cell transplantation with rehabilitation therapy presents an effective stroke treatment. Here, we discuss current breakthroughs in stem cell research along with rehabilitation strategies that may have a synergistic outcome when combined together after stroke. Indeed, stem cell transplantation offers a promising new approach and may add to current rehabilitation therapies. By reviewing the pathophysiology of stroke and the mechanisms by which stem cells and rehabilitation attenuate this inflammatory process, we hypothesize that a combined therapy will provide better functional outcomes for patients. Using current preclinical data, we explore the prominent types of stem cells, the existing theories for stem cell repair, rehabilitation treatments inside the brain, rehabilitation modalities outside the brain, and evidence pertaining to the benefits of combined therapy. In this review article, we assess the advantages and disadvantages of using stem cell transplantation with rehabilitation to mitigate the devastating effects of stroke.
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Affiliation(s)
- Reed Berlet
- Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd, North Chicago, IL 60064, USA;
| | - Stefan Anthony
- Lake Erie College of Osteopathic Medicine, 5000 Lakewood Ranch Boulevard, Bradenton, FL 34211, USA;
| | - Beverly Brooks
- Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA; (B.B.); (Z.-J.W.)
| | - Zhen-Jie Wang
- Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA; (B.B.); (Z.-J.W.)
| | | | - Alex Shear
- University of Florida, 205 Fletcher Drive, Gainesville, FL 32611, USA;
| | - Blaise Cozene
- Tulane University, 6823 St. Charles Ave, New Orleans, LA 70118, USA;
| | | | - Blake Parsons
- Washington and Lee University, 204 W Washington St, Lexington, VA 24450, USA;
| | - Felipe Esparza Salazar
- Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Campus Norte, Huixquilucan 52786, Mexico; (F.E.S.); (A.R.L.T.); (G.R.M.)
| | - Alma R. Lezama Toledo
- Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Campus Norte, Huixquilucan 52786, Mexico; (F.E.S.); (A.R.L.T.); (G.R.M.)
| | - Germán Rivera Monroy
- Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Campus Norte, Huixquilucan 52786, Mexico; (F.E.S.); (A.R.L.T.); (G.R.M.)
| | | | - Cesario V. Borlongan
- Department of Neurosurgery and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA; (B.B.); (Z.-J.W.)
- Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce B Downs Blvd, Tampa, FL 33612, USA
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Takahashi EA, Kilari S, Misra S. Novel Clinical Therapies and Technologies in Dialysis Vascular Access. KIDNEY360 2021; 2:1373-1379. [PMID: 35369655 PMCID: PMC8676382 DOI: 10.34067/kid.0002962021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Accepted: 06/10/2021] [Indexed: 02/08/2023]
Abstract
The hemodialysis population continues to grow. Although procedures for dialysis have existed for >60 years, significant challenges with vascular access to support hemodialysis persist. Failure of arteriovenous fistulas (AVFs) to mature, loss of AVF and graft patency, thrombosis, and infection hinder long-term access, and add extra health care costs and patient morbidity. There have been numerous innovations over the last decade aimed at addressing the issues. In this study, we review the literature and summarize the recent evolution of drug delivery, graft development, minimally invasive AVF creation, and stem-cell therapy for hemodialysis access.
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Affiliation(s)
| | | | - Sanjay Misra
- Department of Radiology, Mayo Clinic, Rochester, Minnesota
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50
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Li K, Shi G, Lei X, Huang Y, Li X, Bai L, Qin C. Age-related alteration in characteristics, function, and transcription features of ADSCs. Stem Cell Res Ther 2021; 12:473. [PMID: 34425900 PMCID: PMC8383427 DOI: 10.1186/s13287-021-02509-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/13/2021] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Adipose tissue-derived stem cells (ADSCs) autologous transplantation has been a promising strategy for aging-related disorders. However, the relationship between ADSCs senescence and organismal aging has not been clearly established. Therefore, we aimed at evaluating senescence properties of ADSCs from different age donors and to verify the influence of organismal aging on the proliferation and function of ADSCs in vitro, providing the theoretical basis for the clinical application of autologous ADSCs transplantation. METHODS AND RESULTS The ADSCs were obtained from 1-month-old and 20-month-old mice. The cells characteristics, functions, gene expression levels, apoptosis proportion, cell cycle, SA-β-gal staining, and transcription features were evaluated. Compared to ADSCs from 1-month-old mice, ADSCs from 20-month-old mice exhibited some senescence-associated changes, including inhibited abilities to proliferate. Moreover, differentiation abilities, cell surface markers, and cytokines secreting differed between 1M and 20M ADSCs. SA-β-Gal staining did not reveal differences between the two donor groups, while cells exhibited more remarkable age-related changes through continuous passages. Based on transcriptome analysis and further detection, the CCL7-CCL2-CCR2 axis is the most probable mechanism for the differences. CONCLUSIONS ADSCs from old donors have some age-related alterations. The CCL7-CCL2-CCR2 axis is a potential target for gene therapy to reduce the harmful effects of ADSCs from old donors. To improve on autologous transplantation, we would recommend that ADSCs should be cryopreserved in youth with a minimum number of passages or block CCL7-CCL2-CCR2 to abolish the effects of age-related alterations in ADSCs through the Chemokine signaling pathway.
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Affiliation(s)
- Keya Li
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China
| | - Guiying Shi
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China
| | - Xuepei Lei
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China
| | - Yiying Huang
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China
| | - Xinyue Li
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China
| | - Lin Bai
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.
| | - Chuan Qin
- Key Laboratory of Human Disease Comparative Medicine, Chinese Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, No.5 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People's Republic of China.
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