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Zou B, Wang D, Zhong J, He Z, Zhou Y, Yang H, Liu Y, Zeng G, Duan X. Mesenchymal stem cells attenuate hyperoxaluria-induced kidney injury and crystal depositions via inhibiting the activation of NLRP3 inflammasome. Life Sci 2025; 371:123608. [PMID: 40194762 DOI: 10.1016/j.lfs.2025.123608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Revised: 03/16/2025] [Accepted: 04/01/2025] [Indexed: 04/09/2025]
Abstract
AIMS Calcium oxalate (CaOx) is the predominant form of kidney stones, associated with significant morbidity and recurrence rates. Mesenchymal stem cells (MSCs) have shown promise in treating renal injury, but their impact on CaOx stone formation remains unclear. MATERIALS AND METHODS We established a hyperoxaluria-induced AKI model in mice through intraperitoneal injection of glyoxylate. Two types of MSCs, bone marrow-derived MSCs (BMSCs) and umbilical cord-derived mesenchymal stem cells (UMSCs), were injected through tail vein injection. Histological evaluations and blood biochemical tests were performed to assess crystal deposition and kidney function. The inflammatory response and NLRP3 inflammasome activation were assessed using immunofluorescence, immunohistochemistry, TUNEL staining, and qPCR. In vitro, macrophages were cocultured in the presence of MSCs. ELISA was used to measure IL-1β and IL-18 release. MTS assays assessed renal epithelial cell protection. Western blotting evaluated NLRP3 inflammasome activation in macrophages. KEY FINDINGS Both BMSCs and UMSCs significantly inhibited CaOx crystal deposition and kidney injury by inhibiting NLRP3 inflammasome activation. In vitro, both MSC types suppressed NLRP3 inflammasome activation in macrophages through the NF-κB signaling pathway, leading to decreased release of IL-1β and IL-18 and enhanced protection of renal epithelial cells. This attenuation of renal tubular cell injury is a critical factor in preventing CaOx stone formation. SIGNIFICANCE Our findings reveal that Both BMSCs and UMSCs effectively attenuate hyperoxaluria-induced kidney injury and crystal deposition by inhibiting NLRP3 inflammasome activation. This discovery is helpful for developing new effective therapeutic means for nephrolithiasis.
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Affiliation(s)
- Bangyu Zou
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University; Department of Urology, Changhai Hospital, First Affiliated Hospital of Naval Medical University, Shanghai, China
| | - Ding Wang
- Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Jinghua Zhong
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University
| | - Zhiqing He
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University
| | - Yuhao Zhou
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University
| | - Houmeng Yang
- Department of Urology, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo, China
| | - Yongda Liu
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University
| | - Guohua Zeng
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University.
| | - Xiaolu Duan
- Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Guangdong Provincial Key Laboratory of Urological Diseases, Guangzhou, China; Guangdong Engineering Research Center of Urinary Minimally Invasive Surgery Robot and Intelligent Equipment, Guangzhou, China; Guangzhou Institute of Urology, Guangzhou Medical University.
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Kaplan N, Kabatas S, Civelek E, Savrunlu EC, Akkoc T, Boyalı O, Öztürk E, Can H, Genc A, Karaöz E. Multiroute administration of Wharton’s jelly mesenchymal stem cells in chronic complete spinal cord injury: A phase I safety and feasibility study. World J Stem Cells 2025; 17:101675. [DOI: 10.4252/wjsc.v17.i5.101675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Revised: 01/09/2025] [Accepted: 03/27/2025] [Indexed: 05/26/2025] Open
Abstract
BACKGROUND Traumatic spinal cord injury (SCI) is a life-altering condition that results in long-term complications, including progressive neurodegeneration and cord atrophy. It presents a significant unmet medical need with extensive social and economic burdens.
AIM To evaluate the safety and preliminary efficacy of allogeneic mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs) in patients with chronic complete SCI. The primary objective was to assess whether WJ-MSCs could facilitate neurological recovery and improve the quality of life in this patient population.
METHODS This open-label, multicenter phase I study investigated the effects of administering WJ-MSCs via three delivery routes: Intrathecal (for localized spinal targeting); intramuscular (for targeting end organ); and intravenous (for systemic immunomodulation). While all three routes were used concurrently to enhance therapeutic synergy, neurological, sensory, and functional scales were used to assess overall efficacy. Participants with chronic SCI (duration of at least 6 months) who had significant impairment and disability were eligible for inclusion. WJ-MSCs were administered twice monthly for 2 months, with each route receiving a dose of 1 × 106 cells/kg. Patients were closely monitored for 1 year following treatment.
RESULTS At baseline, participants displayed considerable functional deficits, as indicated by the following scores: Functional independence measure of 77.5 ± 2.26; Modified Ashworth Scale of 15.83 ± 4.83; American Spinal Injury Association (ASIA) Motor score of 1.67 ± 2.66; ASIA Light Touch and Pin-Prick scores of 62 ± 18.42 each; Wexner Incontinence Score of 20; and Qualiveen Short Form, a validated questionnaire specifically designed to assess the impact of urinary dysfunction on quality of life in individuals with SCI, score of 32. Following WJ-MSC therapy, significant improvements were observed in all neurological functions over the 1-year follow-up. Notably, the ASIA Motor score improved significantly (χ2 = 23.938, P < 0.001), and Qualiveen Short Form scores demonstrated a substantial enhancement in quality of life (z = -2.214, P < 0.05).
CONCLUSION This phase I study, conducted without a control group, suggests that the administration of WJ-MSCs through multiple routes is both safe and potentially effective in patients with chronic complete SCI. However, the observed neurological improvements cannot be solely attributed to WJ-MSC therapy, as concurrent pharmacological and rehabilitative interventions were not controlled. These findings indicated that WJ-MSC therapy may offer a promising approach for enhancing neurological function and quality of life in this challenging patient population. Further research with larger cohorts and extended follow-up is necessary to validate these preliminary results.
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Affiliation(s)
- Necati Kaplan
- Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Tekirdağ 59860, Türkiye
| | - Serdar Kabatas
- Department of Neurosurgery, University of Health Sciences Türkiye, Gaziosmanpaşa Training and Research Hospital, Istanbul 34255, Türkiye
- Center for Stem Cell & Gene Therapy Research and Practice, University of Health Sciences Türkiye, İstanbul 34255, Türkiye
| | - Erdinç Civelek
- Department of Neurosurgery, University of Health Sciences Türkiye, Gaziosmanpaşa Training and Research Hospital, Istanbul 34255, Türkiye
| | | | - Tolga Akkoc
- Tubitak Marmara Research Center, Genetic Engineering and Biotechnology Institute, Kocaeli 41470, Türkiye
| | - Osman Boyalı
- Department of Neurosurgery, University of Health Sciences Türkiye, Gaziosmanpaşa Training and Research Hospital, Istanbul 34255, Türkiye
| | - Erek Öztürk
- Department of Neurosurgery, Orthopaediezentrum Magdeburg, Magdeburg 39112, Saxony-Anhalt, Germany
| | - Halil Can
- Department of Neurosurgery, Atlas University, İstanbul 34408, Türkiye
| | - Ali Genc
- Department of Neurosurgery, Palmiye Hospital, Hatay 31200, Türkiye
| | - Erdal Karaöz
- Center for Regenerative Medicine and Stem Cell Research & Manufacturing, Liv Hospital, Istanbul 34340, Türkiye
- Department of Histology and Embryology, Istinye University, Faculty of Medicine, Zeytinburnu 34010, Istanbul, Türkiye
- Istinye University, Center for Stem Cell and Tissue Engineering Research and Practice, Beşiktaş 34340, Istanbul, Türkiye
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Ali A, Kuo WW, Kuo CH, Lo JF, Hsieh DJY, Pai P, Ho TJ, Shibu MA, Lin SZ, Huang CY. Chaperone-assisted E3 ligase-engineered mesenchymal stem cells target hyperglycemia-induced p53 for ubiquitination and proteasomal degradation ameliorates self-renewal. Biol Res 2025; 58:20. [PMID: 40270049 PMCID: PMC12020092 DOI: 10.1186/s40659-025-00604-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2025] [Accepted: 04/09/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Stem cell therapies may potentially be used in regenerative and reconstructive medicine due to their ability for self-renewal and differentiation. Stressful conditions, such as hyperglycemia, adversely affect stem cell functions, impairing their function and promoting differentiation by opposing self-renewal. The carboxyl terminus of HSP70 interacting protein (CHIP), which is a cochaperone and E3 ligase, maintains protein homeostasis and performs quality control of the cell via ubiquitylation. However, the role of CHIP in regulating stemness remains unknown. RESULTS Hyperglycemia downregulated CHIP-induced p53, arrested the cell cycle at the gap (G1) phase, and promoted the loss of stemness in WJMSCs. Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, immunofluorescence, and cell cycle analysis showed that CHIP-overexpressing WJMSCs downregulated the expression of phosphorylated p53 and shortened its half-life while enhancing self-renewal factors. Additionally, co-IP and Western blotting revealed that CHIP promoted the ubiquitination and proteasomal degradation of hyperglycemia-induced p53 through the chaperone system. CONCLUSIONS CHIP may promote ubiquitin-mediated proteasomal degradation of hyperglycemia-induced p53 rescues self-renewal genes, which can maintain the long-term undifferentiated state of WJMSCs. CHIP may be an alternative therapeutic option in regenerative medicine for hyperglycemic-related complications in diabetes.
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Affiliation(s)
- Ayaz Ali
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
- Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan
| | - Wei-Wen Kuo
- Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan
| | - Chia-Hua Kuo
- Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan
| | - Jeng-Feng Lo
- Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
| | | | - Peiying Pai
- School of Medicine, College of Medicine, China Medical University, Taichung, 40402, Taiwan
- Division of Cardiovascular Medicine, Department of Medicine, China Medical University Hospital, Taichung, 40447, Taiwan
| | - Tsung-Jung Ho
- Department of Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | | | - Shinn-Zong Lin
- Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan
- Department of Neurosurgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, 970, Taiwan
| | - Chih-Yang Huang
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan.
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
- Department of Biotechnology, Asia University, Taichung, Taiwan.
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
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Yu Y, Tao Y, Ma J, Li J, Song Z. Targeting the tumor microenvironment with mesenchymal stem cells based delivery approach for efficient delivery of anticancer agents: An updated review. Biochem Pharmacol 2025; 232:116725. [PMID: 39746456 DOI: 10.1016/j.bcp.2024.116725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/14/2024] [Accepted: 12/18/2024] [Indexed: 01/04/2025]
Abstract
Drug delivery to cancer cells continues to present a major therapeutic challenge. Mesenchymal stem cells (MSCs) possess an intrinsic ability to migrate specifically to tumor tissues, making them promising candidates for targeted drug delivery. Evidence from preclinical studies indicates that MSCs loaded with therapeutic anti-cancer agents exhibit considerable anti-tumor activity. Moreover, several clinical trials are currently evaluating their effectiveness in cancer patients. The integration of MSCs with synthetic nanoparticles (NPs) enhances their therapeutic potential, particularly through the use of cell membrane-coated NPs, which represent a significant advancement in the field. This review systematically investigates the tumor microenvironment, the sources of MSCs, the tumor homing mechanisms, and the methods of loading and releasing anticancer drugs from MSCs. Furthermore, cutting-edge strategies to improve the efficacy of MSCs based drug delivery systems (DDS) including the innovative use of MSC membrane coated nanoparticles have been discussed. The study concludes with an overview of the therapeutic use of MSCs as drug carriers, including a detailed analysis of the mechanisms by which MSCs deliver therapeutics to cancer cells, enabling targeted drug delivery. It aims to elucidate the current state of this approach, identify key areas for development, and outline potential future directions for advancing MSCs based cancer therapies.
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Affiliation(s)
- Yang Yu
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Ying Tao
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130000, China
| | - Jingru Ma
- Department of Clinical Laboratory, the Second Hospital of Jilin University, Changchun 130000, China
| | - Jian Li
- Department of Emergency and Critical Care, the Second Hospital of Jilin University, Changchun 130000, China
| | - Zhidu Song
- Department of Ophthalmology, the Second Hospital of Jilin University, Changchun 130000, China.
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Salah B, Shahin D, Sarhan M, Al-Karmi J, Al-Kurdi B, Al-Atoom R, Ismail MA, Hammad N, Jafar H, Awidi A, Ababneh NA. Effect of cigarette smoke on the proliferation, viability, gene expression, and cellular functions of adipose-derived mesenchymal stem cells from smoking and non-smoking donors. Biol Open 2024; 13:bio061665. [PMID: 39625294 PMCID: PMC11646114 DOI: 10.1242/bio.061665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2024] [Accepted: 10/11/2024] [Indexed: 12/16/2024] Open
Abstract
Cigarette smoking negatively impacts mesenchymal stem cell functionality, including proliferation, viability, and differentiation potential. Adipose-derived mesenchymal stem cells (ADMSCs) are increasingly used for therapeutic purposes, but the specific effects of smoking in vivo on these cells are poorly understood. This study investigates the effects of cigarette smoke on the proliferation, viability, gene expression, and cellular functions of ADMSCs from smoking and non-smoking donors. In this study, ADMSCs were isolated from healthy smokers and non-smokers, and cell proliferation was assessed using the MTT assay, viability with apoptosis assays, mitochondrial membrane potential (MMP), and gene expression related to oxidative stress and cellular functions. Cell cycle analysis was also conducted. Our findings reveal a significant decrease in the proliferation of ADMSCs from smokers. Apoptosis assays showed reduced viable cells in smokers without a significant change in MMP, suggesting alternative pathways contributing to decreased viability. Gene expression analysis indicated the upregulation of genes associated with oxidative stress response and cellular defense mechanisms and the downregulation of genes related to inflammatory signaling, detoxification, and cellular metabolism. Cell cycle analysis indicates cycle arrest or delay in smokers, possibly due to stress and potential DNA damage. Smoking negatively affects ADMSCs' proliferation, viability, and function through oxidative stress and gene expression alterations. These findings highlight the importance of considering smoking status in ADMSC therapies and the need for further research to mitigate the effect of smoking on stem cells.
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Affiliation(s)
- Bareqa Salah
- General Surgery Department/Plastic & Reconstructive, Jordan University Hospital, the University of Jordan, 11942
| | - Diana Shahin
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
| | - Momen Sarhan
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
- School of Medicine, the University of Jordan, Amman, Jordan, 11942
| | - Joud Al-Karmi
- School of Medicine, the University of Jordan, Amman, Jordan, 11942
| | - Ban Al-Kurdi
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
| | - Renata Al-Atoom
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
| | | | - Nouran Hammad
- School of Medicine, Jordan University of Science and Technology, Al-Ramtha, Jordan, 22110
| | - Hanan Jafar
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
| | - Abdalla Awidi
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
- Hemostasis and Thrombosis Laboratory, School of Medicine, the University of Jordan, Amman, Jordan, 11942
- Department of Hematology and Oncology, Jordan University Hospital, Amman, Jordan, 11492
| | - Nidaa A. Ababneh
- Cell Therapy Center, the University of Jordan, Amman, Jordan, 11942
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Zhidu S, Ying T, Rui J, Chao Z. Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities. Stem Cell Res Ther 2024; 15:266. [PMID: 39183341 PMCID: PMC11346273 DOI: 10.1186/s13287-024-03885-z] [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: 05/17/2024] [Accepted: 08/14/2024] [Indexed: 08/27/2024] Open
Abstract
Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.
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Affiliation(s)
- Song Zhidu
- Department of Ophthalmology, the Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun City, Jilin Province, China
| | - Tao Ying
- Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Jiang Rui
- Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Zhang Chao
- Department of Ophthalmology, the Second Hospital of Jilin University, No. 218, Ziqiang Street, Nanguan District, Changchun City, Jilin Province, China.
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Shi L, Chen L, Gao X, Sun X, Jin G, Yang Y, Shao Y, Zhu F, Zhou G. Comparison of different sources of mesenchymal stem cells: focus on inflammatory bowel disease. Inflammopharmacology 2024; 32:1721-1742. [PMID: 38615278 DOI: 10.1007/s10787-024-01468-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 03/22/2024] [Indexed: 04/15/2024]
Abstract
Inflammatory bowel disease (IBD) poses a significant challenge in modern medicine, with conventional treatments limited by efficacy and associated side effects, necessitating innovative therapeutic approaches. Mesenchymal stem cells (MSC) have emerged as promising candidates for IBD treatment due to their immunomodulatory properties and regenerative potential. This thesis aims to explore and compare various sources of MSC and evaluate their efficacy in treating IBD. This study comprehensively analyses MSC derived from multiple sources, including bone marrow, adipose tissue, umbilical cord, and other potential reservoirs. Core elements of this investigation include assessing differences in cell acquisition, immunomodulatory effects, and differentiation capabilities among these MSC sources, as well as comparing their clinical trial outcomes in IBD patients to their therapeutic efficacy in animal models. Through meticulous evaluation and comparative analysis, this thesis aims to elucidate disparities in the efficacy of different MSC sources for IBD treatment, thereby identifying the most promising therapeutic applications. The findings of this study are intended to advance our understanding of MSC biology and offer valuable insights for selecting the most effective MSC sources for personalized IBD therapy. Ultimately, this research endeavor will optimise therapeutic strategies for managing inflammatory bowel disease through the utilization of MSC.
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Affiliation(s)
- Lihao Shi
- Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Leilei Chen
- Cheeloo College of Medicine, Shandong University, Jinan, 250012, China
| | - Xizhuang Gao
- Clinical Medical College of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People's Republic of China
| | - Xufan Sun
- Clinical Medical College of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People's Republic of China
| | - Guiyuan Jin
- Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People's Republic of China
| | - Yonghong Yang
- Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, People's Republic of China
| | - Yiming Shao
- Department of Burns and Plastic Surgery, Affiliated Hospital of Jining Medical University, Jining, China
| | - Fengqin Zhu
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People's Republic of China
| | - Guangxi Zhou
- Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.
- Department of Gastroenterology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, 272000, People's Republic of China.
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8
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Zhang L. The Role of Mesenchymal Stem Cells in Modulating the Breast Cancer Microenvironment. Cell Transplant 2023; 32:9636897231220073. [PMID: 38135917 DOI: 10.1177/09636897231220073] [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: 12/24/2023] Open
Abstract
The role of mesenchymal stem cells (MSCs) in the breast tumor microenvironment (TME) is significant and multifaceted. MSCs are recruited to breast tumor sites through molecular signals released by tumor sites. Once in the TME, MSCs undergo polarization and interact with various cell populations, including immune cells, cancer-associated fibroblasts (CAFs), cancer stem cells (CSCs), and breast cancer cells. In most cases, MSCs play roles in breast cancer therapeutic resistance, but there is also evidence that indicates their abilities to sensitize cancer cells to chemotherapy and radiotherapy. MSCs possess inherent regenerative and homing properties, making them attractive candidates for cell-based therapies. Therefore, MSCs can be engineered to express therapeutic molecules or deliver anti-cancer agents directly to tumor sites. Unraveling the intricate relationship between MSCs and the breast TME has the potential to uncover novel therapeutic targets and advance our understanding of breast cancer biology.
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Affiliation(s)
- Luxiao Zhang
- Department of Surgical Oncology, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
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Hohenwallner K, Troppmair N, Panzenboeck L, Kasper C, El Abiead Y, Koellensperger G, Lamp LM, Hartler J, Egger D, Rampler E. Decoding Distinct Ganglioside Patterns of Native and Differentiated Mesenchymal Stem Cells by a Novel Glycolipidomics Profiling Strategy. JACS AU 2022; 2:2466-2480. [PMID: 36465531 PMCID: PMC9709940 DOI: 10.1021/jacsau.2c00230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 10/01/2022] [Accepted: 10/03/2022] [Indexed: 06/17/2023]
Abstract
Gangliosides are an indispensable glycolipid class concentrated on cell surfaces with a critical role in stem cell differentiation. Nonetheless, owing to the lack of suitable methods for scalable analysis covering the full scope of ganglioside molecular diversity, their mechanistic properties in signaling and differentiation remain undiscovered to a large extent. This work introduces a sensitive and comprehensive ganglioside assay based on liquid chromatography, high-resolution mass spectrometry, and multistage fragmentation. Complemented by an open-source data evaluation workflow, we provide automated in-depth lipid species-level and molecular species-level annotation based on decision rule sets for all major ganglioside classes. Compared to conventional state-of-the-art methods, the presented ganglioside assay offers (1) increased sensitivity, (2) superior structural elucidation, and (3) the possibility to detect novel ganglioside species. A major reason for the highly improved sensitivity is the optimized spectral readout based on the unique capability of two parallelizable mass analyzers for multistage fragmentation. We demonstrated the high-throughput universal capability of our novel analytical strategy by identifying 254 ganglioside species. As a proof of concept, 137 unique gangliosides were annotated in native and differentiated human mesenchymal stem cells including 78 potential cell-state-specific markers and 38 previously unreported gangliosides. A general increase of the ganglioside numbers upon differentiation was observed as well as cell-state-specific clustering based on the ganglioside species patterns. The combination of the developed glycolipidomics assay with the extended automated annotation tool enables comprehensive in-depth ganglioside characterization as shown on biological samples of interest. Our results suggest ganglioside patterns as a promising quality control tool for stem cells and their differentiation products. Additionally, we believe that our analytical workflow paves the way for probing glycolipid-based biochemical processes shedding light on the enigmatic processes of gangliosides and glycolipids in general.
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Affiliation(s)
- Katharina Hohenwallner
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
- Vienna
Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna 1090, Austria
| | - Nina Troppmair
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
- Vienna
Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna 1090, Austria
| | - Lisa Panzenboeck
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
- Vienna
Doctoral School in Chemistry (DoSChem), University of Vienna, Vienna 1090, Austria
| | - Cornelia Kasper
- Institute
of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Vienna 1190, Austria
| | - Yasin El Abiead
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
| | - Gunda Koellensperger
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
| | - Leonida M. Lamp
- Institute
of Pharmaceutical Sciences, University of
Graz, Graz 8010, Austria
| | - Jürgen Hartler
- Institute
of Pharmaceutical Sciences, University of
Graz, Graz 8010, Austria
- Field
of Excellence BioHealth − University
of Graz, Graz 8010, Austria
| | - Dominik Egger
- Institute
of Cell and Tissue Culture Technologies, University of Natural Resources and Life Sciences, Vienna 1190, Austria
| | - Evelyn Rampler
- Department
of Analytical Chemistry, Faculty of Chemistry, University of Vienna, Vienna 1090, Austria
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Hade MD, Suire CN, Mossell J, Suo Z. Extracellular vesicles: Emerging frontiers in wound healing. Med Res Rev 2022; 42:2102-2125. [PMID: 35757979 DOI: 10.1002/med.21918] [Citation(s) in RCA: 64] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 12/10/2021] [Accepted: 06/07/2022] [Indexed: 12/19/2022]
Abstract
Extracellular vesicles are membranous particles, ranging from 30 nm to 10 µm in diameter, which are released by nearly all cell types to aid in intercellular communication. These complex vesicles carry a multitude of signaling moieties from their cell of origin, such as proteins, lipids, cell surface receptors, enzymes, cytokines, metabolites, and nucleic acids. A growing body of evidence suggests that in addition to delivering cargos into target cells to facilitate intercellular communication, extracellular vesicles may also play roles in such processes as cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. As these vesicles have natural biocompatibility, stability in circulation, low toxicity, and low immunogenicity, and serve as efficient carriers of molecular cargos, these nanoparticles are ideal therapeutic candidates for regenerative medicine. Exploring and identifying the homeostatic functions of extracellular vesicles may facilitate the development of new regenerative therapies. In this review, we summarize the wound healing process, difficulties in stem cell therapies for regenerative medicine, and the applications of mesenchymal stromal cell-derived extracellular vesicles in improving and accelerating the wound healing process.
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Affiliation(s)
- Mangesh D Hade
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - Caitlin N Suire
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - James Mossell
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
| | - Zucai Suo
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida, USA
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11
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Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, Nguyen GH, Le PTT, Hoang VT, Forsyth NR, Heke M, Nguyen LT. Stem cell-based therapy for human diseases. Signal Transduct Target Ther 2022; 7:272. [PMID: 35933430 PMCID: PMC9357075 DOI: 10.1038/s41392-022-01134-4] [Citation(s) in RCA: 451] [Impact Index Per Article: 150.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 07/19/2022] [Accepted: 07/21/2022] [Indexed: 02/07/2023] Open
Abstract
Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.
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Affiliation(s)
- Duc M Hoang
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam.
| | - Phuong T Pham
- Department of Cellular Therapy, Vinmec High-Tech Center, Vinmec Healthcare System, Hanoi, Vietnam
| | - Trung Q Bach
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Anh T L Ngo
- Department of Cellular Therapy, Vinmec High-Tech Center, Vinmec Healthcare System, Hanoi, Vietnam
| | - Quyen T Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Trang T K Phan
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Giang H Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Phuong T T Le
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Van T Hoang
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
| | - Nicholas R Forsyth
- Institute for Science & Technology in Medicine, Keele University, Keele, UK
| | - Michael Heke
- Department of Biology, Stanford University, Stanford, CA, USA
| | - Liem Thanh Nguyen
- Department of Research and Development, Vinmec Research Institute of Stem Cell and Gene Technology, Vinmec Healthcare System, Hanoi, Vietnam
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12
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Rahbaran M, Zekiy AO, Bahramali M, Jahangir M, Mardasi M, Sakhaei D, Thangavelu L, Shomali N, Zamani M, Mohammadi A, Rahnama N. Therapeutic utility of mesenchymal stromal cell (MSC)-based approaches in chronic neurodegeneration: a glimpse into underlying mechanisms, current status, and prospects. Cell Mol Biol Lett 2022; 27:56. [PMID: 35842587 PMCID: PMC9287902 DOI: 10.1186/s11658-022-00359-z] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Accepted: 06/30/2022] [Indexed: 12/11/2022] Open
Abstract
Recently, mesenchymal stromal cell (MSC)-based therapy has become an appreciated therapeutic approach in the context of neurodegenerative disease therapy. Accordingly, a myriad of studies in animal models and also some clinical trials have evinced the safety, feasibility, and efficacy of MSC transplantation in neurodegenerative conditions, most importantly in Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). The MSC-mediated desired effect is mainly a result of secretion of immunomodulatory factors in association with release of various neurotrophic factors (NTFs), such as glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF). Thanks to the secretion of protein-degrading molecules, MSC therapy mainly brings about the degradation of pathogenic protein aggregates, which is a typical appearance of chronic neurodegenerative disease. Such molecules, in turn, diminish neuroinflammation and simultaneously enable neuroprotection, thereby alleviating disease pathological symptoms and leading to cognitive and functional recovery. Also, MSC differentiation into neural-like cells in vivo has partially been evidenced. Herein, we focus on the therapeutic merits of MSCs and also their derivative exosome as an innovative cell-free approach in AD, HD, PD, and ALS conditions. Also, we give a brief glimpse into novel approaches to potentiate MSC-induced therapeutic merits in such disorders, most importantly, administration of preconditioned MSCs.
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Affiliation(s)
- Mohaddeseh Rahbaran
- Biotechnology Department, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran
| | - Angelina Olegovna Zekiy
- Department of Prosthetic Dentistry, I. M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
| | - Mahta Bahramali
- Biotechnology Department, University of Tehran, Tehran, Iran
| | | | - Mahsa Mardasi
- Biotechnology Department, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Delaram Sakhaei
- School of Medicine, Sari Branch, Islamic Azad University, Sari, Iran
| | - Lakshmi Thangavelu
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, India
| | - Navid Shomali
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Zamani
- Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
| | - Ali Mohammadi
- Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran.
| | - Negin Rahnama
- Department of Internal Medicine and Health Services, Semnan University of Medical Sciences, Semnan, Iran.
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13
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Park YS, Park BW, Choi H, Lee SH, Kim M, Park HJ, Kim IB. Chorion-derived perinatal mesenchymal stem cells improve cardiac function and vascular regeneration: preferential treatment for ischemic heart disease. Hellenic J Cardiol 2022; 66:52-58. [DOI: 10.1016/j.hjc.2022.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 05/24/2022] [Accepted: 05/24/2022] [Indexed: 11/04/2022] Open
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14
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Barlian A, Saputri DHA, Hernando A, Khoirinaya C, Prajatelistia E, Tanoto H. Spidroin striped micropattern promotes chondrogenic differentiation of human Wharton's jelly mesenchymal stem cells. Sci Rep 2022; 12:4837. [PMID: 35319008 PMCID: PMC8941093 DOI: 10.1038/s41598-022-08982-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 03/14/2022] [Indexed: 11/29/2022] Open
Abstract
Cartilage tissue engineering, particularly micropattern, can influence the biophysical properties of mesenchymal stem cells (MSCs) leading to chondrogenesis. In this research, human Wharton’s jelly MSCs (hWJ-MSCs) were grown on a striped micropattern containing spider silk protein (spidroin) from Argiope appensa. This research aims to direct hWJ-MSCs chondrogenesis using micropattern made of spidroin bioink as opposed to fibronectin that often used as the gold standard. Cells were cultured on striped micropattern of 500 µm and 1000 µm width sizes without chondrogenic differentiation medium for 21 days. The immunocytochemistry result showed that spidroin contains RGD sequences and facilitates cell adhesion via integrin β1. Chondrogenesis was observed through the expression of glycosaminoglycan, type II collagen, and SOX9. The result on glycosaminoglycan content proved that 1000 µm was the optimal width to support chondrogenesis. Spidroin micropattern induced significantly higher expression of SOX9 mRNA on day-21 and SOX9 protein was located inside the nucleus starting from day-7. COL2A1 mRNA of spidroin micropattern groups was downregulated on day-21 and collagen type II protein was detected starting from day-14. These results showed that spidroin micropattern enhances chondrogenic markers while maintains long-term upregulation of SOX9, and therefore has the potential as a new method for cartilage tissue engineering.
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Affiliation(s)
- Anggraini Barlian
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia. .,Research Center for Nanosciences and Nanotechnology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia.
| | - Dinda Hani'ah Arum Saputri
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Adriel Hernando
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Candrani Khoirinaya
- School of Life Sciences and Technology, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Ekavianty Prajatelistia
- Faculty of Mechanical and Aerospace Engineering, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
| | - Hutomo Tanoto
- Faculty of Mechanical and Aerospace Engineering, Bandung Institute of Technology, Bandung, West Java, 40132, Indonesia
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15
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Egger D, Lavrentieva A, Kugelmeier P, Kasper C. Physiologic isolation and expansion of human mesenchymal stem/stromal cells for manufacturing of cell-based therapy products. Eng Life Sci 2022; 22:361-372. [PMID: 35382547 PMCID: PMC8961040 DOI: 10.1002/elsc.202100097] [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: 07/30/2021] [Revised: 10/13/2021] [Accepted: 10/15/2021] [Indexed: 01/04/2023] Open
Abstract
The utilization of mesenchymal stem/stromal cells raises new hopes in treatment of diseases and pathological conditions, while at the same time bringing immense challenges for researchers, manufacturers and physicians. It is essential to consider all steps along the in vitro fabrication of cell-based products in order to reach efficient and reproducible treatment outcomes. Here, the optimal protocols for isolation, cultivation and differentiation of mesenchymal stem cells are required. In this review we discuss these aspects and their influence on the final cell-based product quality. We demonstrate that physiological in vitro cell cultivation conditions play a crucial role in therapeutic functionalities of cultivated cells. We show that three-dimensional cell culture, dynamic culture conditions and physiologically relevant in vitro oxygen concentrations during isolation and expansion make a decisive contribution towards the improvement of cell-based products in regenerative medicine.
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Affiliation(s)
- Dominik Egger
- Department of BiotechnologyUniversity of Natural Resources and Life ScienceViennaAustria
| | | | | | - Cornelia Kasper
- Department of BiotechnologyUniversity of Natural Resources and Life ScienceViennaAustria
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16
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Ali A, Kuo W, Kuo C, Lo J, Chen MYC, Daddam JR, Ho T, Viswanadha VP, Shibu MA, Huang C. E3 ligase activity of Carboxyl terminus of Hsc70 interacting protein (CHIP) in Wharton's jelly derived mesenchymal stem cells improves their persistence under hyperglycemic stress and promotes the prophylactic effects against diabetic cardiac damages. Bioeng Transl Med 2021; 6:e10234. [PMID: 34589606 PMCID: PMC8459600 DOI: 10.1002/btm2.10234] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 05/21/2021] [Accepted: 05/23/2021] [Indexed: 01/28/2023] Open
Abstract
Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated. In this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased Carboxyl terminus of Hsc70 interacting protein (CHIP) expression promoted phosphatase and tensin homolog (PTEN) degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Coculturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in embryo derived cardiac cell lines. CHIP overexpressing and PTEN silenced WJMSCs ameliorated diabetic effects in streptozotocin (STZ) induced diabetic rats and further improved their body weight and heart weight, and rescued from hyperglycemia-induced cardiac injury. Considering these, the current study suggests that CHIP confers resistance to apoptosis and acts as a potentiation factor in WJMSCs to provide protection from degenerative effects of diabetes.
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Affiliation(s)
- Ayaz Ali
- Department of Biological Science and TechnologyChina Medical UniversityTaichungTaiwan
| | - Wei‐Wen Kuo
- Department of Biological Science and TechnologyChina Medical UniversityTaichungTaiwan
- Ph.D. Program for Biotechnology Industry, China Medical UniversityTaichungTaiwan
| | - Chia‐Hua Kuo
- Laboratory of Exercise BiochemistryUniversity of TaipeiTaipeiTaiwan
| | - Jeng‐Fan Lo
- Institute of Oral Biology, National Yang‐Ming UniversityTaipeiTaiwan
| | | | - Jayasimha R. Daddam
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationHualienTaiwan
| | - Tsung‐Jung Ho
- Department of Chinese MedicineHualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi UniversityHualienTaiwan
- Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationHualienTaiwan
| | | | - Marthandam Asokan Shibu
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationHualienTaiwan
| | - Chih‐Yang Huang
- Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical FoundationHualienTaiwan
- Graduate Institute of Biomedical Sciences, China Medical UniversityTaichungTaiwan
- Department of Medical ResearchChina Medical University Hospital, China Medical UniversityTaichungTaiwan
- Department of BiotechnologyAsia UniversityTaichungTaiwan
- Center of General Education, Buddhist Tzu Chi Medical FoundationTzu Chi University of Science and TechnologyHualienTaiwan
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17
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Kabataş S, Civelek E, Kaplan N, Savrunlu EC, Sezen GB, Chasan M, Can H, Genç A, Akyuva Y, Boyalı O, Diren F, Karaoz E. Phase I study on the safety and preliminary efficacy of allogeneic mesenchymal stem cells in hypoxic-ischemic encephalopathy. World J Exp Med 2021; 11:17-29. [PMID: 33821203 PMCID: PMC8010270 DOI: 10.5493/wjem.v11.i2.17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 02/19/2021] [Accepted: 03/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in the adult as well as in the neonate, with limited options for treatment and significant dysfunctionality.
AIM To investigate the safety and preliminary efficacy of allogeneic mesenchymal stem cells (MSCs) in HIE patients.
METHODS Patients who had HIE for at least 6 mo along with significant dysfunction and disability were included. All patients were given Wharton’s jelly-derived MSCs at 1 × 106/kg intrathecally, intravenously, and intramuscularly twice a month for two months. The therapeutic effects and prognostic implications of MSCs were evaluated by multiple follow-ups. Functional independence measure (FIM), modified Ashworth, and Karnofsky scales were used to assess any side effects, neurological and cognitive functions, and overall outcomes.
RESULTS The 8 subjects included in the study had a mean age of 33.25 ± 10.18 years. Mean HIE exposure and mean post-HIE durations were 45.63 ± 10.18 and 19.67 ± 29.04 mo, respectively. Mean FIM score was 18.38 ± 1.06, mean modified Ashworth score was 43.5 ± 4.63, and mean Karnofsky score was 20. For the first 24 h, 5 of the patients experienced a subfebrile state, accompanied by mild headaches due to intrathecally administration and muscle pain because of intramuscularly administration. Neurological and functional examinations, laboratory tests, electroencephalography, and magnetic resonance imaging were performed to assess safety of treatment. Mean FIM score increased by 20.88 ± 3.31 in the first month (P = 0.027) and by 31.38 ± 14.69 in 12 mo (P = 0.012). The rate of patients with an FIM score of 126 increased from 14.58% to 16.57% in the first month and 24.90% in 12 mo.
CONCLUSION Multiple triple-route Wharton’s jelly-derived MSC administrations were found to be safe for HIE patients, indicating neurological and functional improvement. Based on the findings obtained here, further randomized and placebo research could be performed.
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Affiliation(s)
- Serdar Kabataş
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
- Pediatric Allergy-Immunology, Marmara University, Institute of Health Sciences, İstanbul 34854, Turkey
- Center for Stem Cell and Gene Therapy Research and Practice, University of Health Sciences, İstanbul 34255, Turkey
| | - Erdinç Civelek
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
- Pediatric Allergy-Immunology, Marmara University, Institute of Health Sciences, İstanbul 34854, Turkey
| | - Necati Kaplan
- Department of Neurosurgery, Istanbul Rumeli University, Çorlu Reyap Hospital, Tekirdağ 59860, Turkey
| | - Eyüp Can Savrunlu
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
| | - Gülseli Berivan Sezen
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
| | - Mourat Chasan
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
| | - Halil Can
- Department of Neurosurgery, İstanbul Biruni University, Faculty of Medicine, İstanbul 34010, Turkey
- Department of Neurosurgery, İstanbul Medicine Hospital, İstanbul 34203, Turkey
| | - Ali Genç
- Department of Neurosurgery, İstanbul Asya Hospital, İstanbul 34250, Turkey
| | - Yener Akyuva
- Department of Neurosurgery, Mustafa Kemal University, Faculty of Medicine, Hatay 31060, Turkey
| | - Osman Boyalı
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
| | - Furkan Diren
- Department of Neurosurgery, University of Health Sciences, Gaziosmanpaşa Training and Research Hospital, İstanbul 34255, Turkey
| | - Erdal Karaoz
- Center for Regenerative Medicine and Stem Cell Research and Manufacturing (LivMedCell), Liv Hospital, İstanbul 34340, Turkey
- Department of Histology and Embryology, İstinye University, Faculty of Medicine, İstanbul 34010, Turkey
- Center for Stem Cell and Tissue Engineering Research and Practice, İstinye University, İstanbul 34340, Turkey
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18
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Witkowska-Zimny M, Majczyna D. How Knowledge about Stem Cells Influences Attitudes towards Breastfeeding: Case Study of Polish Women. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:2382. [PMID: 33804414 PMCID: PMC7967762 DOI: 10.3390/ijerph18052382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 02/22/2021] [Accepted: 02/23/2021] [Indexed: 11/22/2022]
Abstract
Maternal breastfeeding is associated with multiple health benefits, both for the child and the mother. Since breastfeeding rates are declining, finding new, future-oriented strategies to strengthen and support mothers' positive attitudes towards breastfeeding need to be developed. In this paper, we describe how information about the presence of stem cells in breast milk can influence the willingness to breastfeed in the population of Polish pregnant women. A cross-sectional study involving a group of 150 pregnant women was conducted to assess the correlation between their knowledge about stem cells and their attitude towards breastfeeding. Among the respondents, only 6% claimed that they did not know anything about stem cells, but general knowledge about stem cells in the research group was poor. The survey results indicated that city residence, university degree, maternal experience and advanced pregnancy correlated with higher general knowledge regarding stem cells. Most respondents (77.3%) had no knowledge regarding the presence of stem cells in breast milk. Approximately two-thirds of mothers with earlier negative breastfeeding experience declared that information about the presence of stem cells in breast milk could have influenced the decision to continue and extend the time of breastfeeding. Hence highlighting the presence of stem cells in breast milk can be used to encourage breastfeeding as a unique activity.
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Affiliation(s)
- Malgorzata Witkowska-Zimny
- Department of Biophysics and Human Physiology, Medical University of Warsaw, Zwirki i Wigury 61 St, 02-091 Warsaw, Poland;
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19
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Verdugo-Avello FJ, Wychowaniec JK, Jimenez M, Jimenez S, Gutierrez S. Current concepts for tissue transplant services for developing countries. Cell Tissue Bank 2021; 22:323-337. [PMID: 33398493 PMCID: PMC7780911 DOI: 10.1007/s10561-020-09891-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Accepted: 12/08/2020] [Indexed: 10/28/2022]
Abstract
The transplantation of tissues can save lives and re-establish vital functions, where no alternatives of comparable effectiveness exist. This has led to establishment of tissue transplantation as a successful practice worldwide; however, a great variability between countries remains in terms of donation levels, safety, quality of grafts and their efficacy. Tissue transplantation requires coordination of different agencies involved in the implementation of procurement, processing, storage and distribution of tissues and cells from different hospital units that perform surgical procedures with graft-type input requirements. This biomaterial-like requirement has led to the constant development of the area and today these graft products of human origin can be the starting point for new and more advanced biotechnological products. For long-term sustainability and successful transplantation units, a process management comparable to the pharmaceutical industry in terms of quality management systems must be established to produce safe and high-quality human-derived products. This review aims to update the current concepts of tissue transplant services for its application for developing countries using the current Chilean scenario as a case study. We summarize our findings proposing a set of guidelines/actions that should be followed to ensure smooth tissue transplant services implementations with high efficiency and safe use.
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Affiliation(s)
- Francisco J Verdugo-Avello
- Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile. .,LiveMatrix Biotech, Concepción, Chile.
| | | | - Matias Jimenez
- Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.,LiveMatrix Biotech, Concepción, Chile
| | - Silvana Jimenez
- Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile.,LiveMatrix Biotech, Concepción, Chile
| | - Soraya Gutierrez
- Facultad de Ciencias Biológicas, Universidad de Concepción, Concepción, Chile
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20
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Bajetto A, Thellung S, Dellacasagrande I, Pagano A, Barbieri F, Florio T. Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies. Stem Cells Transl Med 2020; 9:1310-1330. [PMID: 32543030 PMCID: PMC7581451 DOI: 10.1002/sctm.20-0161] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/25/2020] [Accepted: 05/30/2020] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs from different origin, and differences in preparation techniques, make difficult to uniform their functional properties for therapeutic purposes. Immunomodulatory, migratory, and differentiation ability, fueled clinical MSC application in regenerative medicine, whereas beneficial effects are currently mainly ascribed to their secretome and extracellular vesicles. MSC translational potential in cancer therapy exploits putative anti-tumor activity and inherent tropism toward tumor sites to deliver cytotoxic drugs. However, controversial results emerged evaluating either the therapeutic potential or homing efficiency of MSCs, as both antitumor and protumor effects were reported. Glioblastoma (GBM) is the most malignant brain tumor and its development and aggressive nature is sustained by cancer stem cells (CSCs) and the identification of effective therapeutic is required. MSC dualistic action, tumor-promoting or tumor-targeting, is dependent on secreted factors and extracellular vesicles driving a complex cross talk between MSCs and GBM CSCs. Tumor-tropic ability of MSCs, besides providing an alternative therapeutic approach, could represent a tool to understand the biology of GBM CSCs and related paracrine mechanisms, underpinning MSC-GBM interactions. In this review, recent findings on the complex nature of MSCs will be highlighted, focusing on their elusive impact on GBM progression and aggressiveness by direct cell-cell interaction and via secretome, also facing the perspectives and challenges in treatment strategies.
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Affiliation(s)
- Adriana Bajetto
- Dipartimento di Medicina InternaUniversità di GenovaGenovaItaly
| | | | | | - Aldo Pagano
- Dipartimento di Medicina SperimentaleUniversità di GenovaGenovaItaly
- IRCCS Ospedale Policlinico San MartinoGenovaItaly
| | | | - Tullio Florio
- Dipartimento di Medicina InternaUniversità di GenovaGenovaItaly
- IRCCS Ospedale Policlinico San MartinoGenovaItaly
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21
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Mahmoudi T, Abdolmohammadi K, Bashiri H, Mohammadi M, Rezaie MJ, Fathi F, Fakhari S, Rezaee MA, Jalili A, Rahmani MR, Tayebi L. Hydrogen Peroxide Preconditioning Promotes Protective Effects of Umbilical Cord Vein Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis. Adv Pharm Bull 2020; 10:72-80. [PMID: 32002364 PMCID: PMC6983995 DOI: 10.15171/apb.2020.009] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Revised: 06/27/2019] [Accepted: 07/02/2019] [Indexed: 12/15/2022] Open
Abstract
Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H2 O2 -preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF). Methods: Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 μM for 24 h) of H2 O2 in vitro. One week following the injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson's trichrome) and expression of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining. Results: Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (P<0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (P<0.05) and diminished expression of TGF-β1 and α-SMA. Conclusion: The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF.
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Affiliation(s)
- Tayebeh Mahmoudi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Kamal Abdolmohammadi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamed Bashiri
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Medical Laboratory Sciences, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mehdi Mohammadi
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Jafar Rezaie
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Fardin Fathi
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Shohreh Fakhari
- Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohammad Ali Rezaee
- Department of Medical Laboratory Sciences, Faculty of Paramedical, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Ali Jalili
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohammad Reza Rahmani
- Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
- Zoonoses Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, WI, 53233, USA
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22
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From 3D to 3D: isolation of mesenchymal stem/stromal cells into a three-dimensional human platelet lysate matrix. Stem Cell Res Ther 2019; 10:248. [PMID: 31399129 PMCID: PMC6688329 DOI: 10.1186/s13287-019-1346-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Revised: 07/02/2019] [Accepted: 07/15/2019] [Indexed: 12/19/2022] Open
Abstract
Background Mesenchymal stem/stromal cells (MSCs) are considered an important candidate in cell therapy and tissue engineering approaches. The culture of stem cells in a 3D environment is known to better resemble the in vivo situation and to promote therapeutically relevant effects in isolated cells. Therefore, the aim of this study was to develop an approach for the direct isolation of MSCs from adipose tissue into a 3D environment, avoiding contact to a 2D plastic surface. Furthermore, the use of a cryoprotective medium for the cryopreservation of whole adipose tissue was evaluated. Materials and methods Cryopreservation of fresh adipose tissue with and without a cryoprotective medium was compared with regard to the viability and metabolic activity of cells. After thawing, the tissue was embedded in a novel human platelet lysate-based hydrogel for the isolation of MSCs. The migration, yield, viability, and metabolic activity of cells from the 3D matrix were compared to cells from 2D explant culture. Also, the surface marker profile and differentiation capacity of MSCs from the 3D matrix were evaluated and compared to MSCs from isolation by enzymatic treatment or 2D explant culture. Results The cryopreservation of whole adipose tissue was found to be feasible, and therefore, adipose tissue can be stored and is available for MSC isolation on demand. Also, we demonstrate the isolation of MSCs from adipose tissue into the 3D matrix. The cells derived from this isolation procedure display a similar phenotype and differentiation capacity like MSCs derived by traditional procedures. Conclusions The presented approach allows to cryopreserve adipose tissue. Furthermore, for the first time, MSCs were directly isolated from the tissue into a soft 3D hydrogel environment, avoiding any contact to a 2D plastic culture surface. Electronic supplementary material The online version of this article (10.1186/s13287-019-1346-2) contains supplementary material, which is available to authorized users.
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23
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Human Amnion Epithelial Cell Therapy for Chronic Liver Disease. Stem Cells Int 2019; 2019:8106482. [PMID: 31485235 PMCID: PMC6702811 DOI: 10.1155/2019/8106482] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 07/24/2019] [Indexed: 12/15/2022] Open
Abstract
Liver fibrosis is a common consequence of chronic liver disease. Over time, liver fibrosis can develop into liver cirrhosis. Current therapies for liver fibrosis are limited, and liver transplant is the only curative therapy for patients who progress to end-stage disease. A potential approach to treat chronic liver disease with increasing interest is cell-based therapy. Among the multiple cell types which have been proposed for therapeutic uses, human amnion epithelial cells and amniotic fluid-derived mesenchymal cells are promising. These cells are highly abundant, and their use poses no ethical concern. Furthermore, they exert potent anti-inflammatory and antifibrotic effects in animal models of liver injury. This review highlights the therapeutic characteristics and discusses how human amnion epithelial cells can be utilised as a therapeutic tool for chronic liver disease.
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24
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Lim R. Concise Review: Fetal Membranes in Regenerative Medicine: New Tricks from an Old Dog? Stem Cells Transl Med 2019; 6:1767-1776. [PMID: 28834402 PMCID: PMC5689753 DOI: 10.1002/sctm.16-0447] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Accepted: 06/16/2017] [Indexed: 12/11/2022] Open
Abstract
The clinical application of the fetal membranes dates back to nearly a century. Their use has ranged from superficial skin dressings to surgical wound closure. The applications of the fetal membranes are constantly evolving, and key to this is the uncovering of multiple populations of stem and stem-like cells, each with unique properties that can be exploited for regenerative medicine. In addition to pro-angiogenic and immunomodulatory properties of the stem and stem-like cells arising from the fetal membranes, the dehydrated and/or decellularized forms of the fetal membranes have been used to support the growth and function of other cells and tissues, including adipose-derived mesenchymal stem cells. This concise review explores the biological origin of the fetal membranes, a history of their use in medicine, and recent developments in the use of fetal membranes and their derived stem and stem-like cells in regenerative medicine. Stem Cells Translational Medicine 2017;6:1767-1776.
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Affiliation(s)
- Rebecca Lim
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.,Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
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25
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Panta W, Imsoonthornruksa S, Yoisungnern T, Suksaweang S, Ketudat-Cairns M, Parnpai R. Enhanced Hepatogenic Differentiation of Human Wharton's Jelly-Derived Mesenchymal Stem Cells by Using Three-Step Protocol. Int J Mol Sci 2019; 20:ijms20123016. [PMID: 31226809 PMCID: PMC6627410 DOI: 10.3390/ijms20123016] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/11/2019] [Accepted: 06/17/2019] [Indexed: 02/06/2023] Open
Abstract
Currently, human Wharton’s jelly-derived mesenchymal stem cells (hWJ-MSCs) are an attractive source of stem cells for cell-based therapy, owing to their ability to undergo self-renewal and differentiate into all mesodermal, some neuroectodermal, and endodermal progenies, including hepatocytes. Herein, this study aimed to investigate the effects of sodium butyrate (NaBu), an epigenetic regulator that directly inhibits histone deacetylase, on hepatic endodermal lineage differentiation of hWJ-MSCs. NaBu, at 1 mM, optimally promoted endodermal differentiation of hWJ-MSCs, along with epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) supplementation. CXCR4, HNF3β, SOX17 (endodermal), and GATA6 (mesendodermal) mRNAs were also up-regulated (p < 0.001). Immunocytochemistry and a Western blot analysis of SOX17 and HNF3β confirmed that the 1 mM NaBu along with EGF and bFGF supplementation condition was appropriately pre-treated with hWJ-MSCs before hepatogenic differentiation. Furthermore, the hepatic differentiation medium with NaBu pre-treatment up-regulated hepatoblast (AFP and HNF3β) and hepatic (CK18 and ALB) markers, and increased the proportion of mature hepatocyte functions, including G6P, C/EBPα, and CYP2B6 mRNAs, glycogen storage and urea secretion. The hepatic differentiation medium with NaBu in the pre-treatment step can induce hWJ-MSC differentiation toward endodermal, hepatoblastic, and hepatic lineages. Therefore, the hepatic differentiation medium with NaBu pre-treatment for differentiating hWJ-MSCs could represent an alternative protocol for cell-based therapy and drug screening in clinical applications.
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Affiliation(s)
- Wachira Panta
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
| | - Sumeth Imsoonthornruksa
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
| | - Ton Yoisungnern
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
| | - Sanong Suksaweang
- School of Pathology and Laboratory Medicine, Institute of Medicine, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
| | - Mariena Ketudat-Cairns
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
| | - Rangsun Parnpai
- Embryo Technology and Stem Cell Research Center, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, Nakhon Ratchasima 30000, Thailand.
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26
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Gaggi G, Izzicupo P, Di Credico A, Sancilio S, Di Baldassarre A, Ghinassi B. Spare Parts from Discarded Materials: Fetal Annexes in Regenerative Medicine. Int J Mol Sci 2019; 20:ijms20071573. [PMID: 30934825 PMCID: PMC6479500 DOI: 10.3390/ijms20071573] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 03/24/2019] [Accepted: 03/26/2019] [Indexed: 12/13/2022] Open
Abstract
One of the main aims in regenerative medicine is to find stem cells that are easy to obtain and are safe and efficient in either an autologous or allogenic host when transplanted. This review provides an overview of the potential use of the fetal annexes in regenerative medicine: we described the formation of the annexes, their immunological features, the new advances in the phenotypical characterization of fetal annexes-derived stem cells, the progressions obtained in the analysis of both their differentiative potential and their secretoma, and finally, the potential use of decellularized fetal membranes. Normally discarded as medical waste, the umbilical cord and perinatal tissue not only represent a rich source of stem cells but can also be used as a scaffold for regenerative medicine, providing a suitable environment for the growth and differentiation of stem cells.
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Affiliation(s)
- Giulia Gaggi
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
| | - Pascal Izzicupo
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
| | - Andrea Di Credico
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
| | - Silvia Sancilio
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
| | - Angela Di Baldassarre
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
| | - Barbara Ghinassi
- Department of Medicine and Aging Sciences, University "G. D'Annunzio" of Chieti-Pescara, 66100 Chieti, Italy.
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27
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Roberts EG, Piekarski BL, Huang K, Emani S, Wong JY, Emani SM. Evaluation of Placental Mesenchymal Stem Cell Sheets for Myocardial Repair and Regeneration. Tissue Eng Part A 2018; 25:867-877. [PMID: 30122114 DOI: 10.1089/ten.tea.2018.0035] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
IMPACT STATEMENT This work explores placental tissue as a cell source for fabrication of tissue-engineered surgical patches for myocardial repair of congenital heart defects. This study demonstrates promising findings for the clinically driven evaluation of the cell source as defined by potential cardiac benefit, compatibility, cell source availability, and implant deliverability. It documents methods for the isolation of mesenchymal stem cells from human placental amnion and chorion tissues, characterization of these cells, and eventual cell sheet growth that can be leveraged going forward for patch fabrication. It establishes support to continue pursuing the placenta as a valuable cell source for myocardial repair.
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Affiliation(s)
- Erin G Roberts
- 1 Department of Materials Science and Engineering, Boston University, Boston, Massachusetts.,2 Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts
| | - Breanna L Piekarski
- 2 Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts
| | - Kevin Huang
- 3 Department of Biomedical Engineering, Boston University, Boston, Massachusetts
| | - Sirisha Emani
- 2 Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts
| | - Joyce Y Wong
- 1 Department of Materials Science and Engineering, Boston University, Boston, Massachusetts.,3 Department of Biomedical Engineering, Boston University, Boston, Massachusetts
| | - Sitaram M Emani
- 2 Department of Cardiovascular Surgery, Children's Hospital, Boston, Massachusetts
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28
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Siniscalco D, Kannan S, Semprún-Hernández N, Eshraghi AA, Brigida AL, Antonucci N. Stem cell therapy in autism: recent insights. STEM CELLS AND CLONING-ADVANCES AND APPLICATIONS 2018; 11:55-67. [PMID: 30425534 PMCID: PMC6204871 DOI: 10.2147/sccaa.s155410] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Autism spectrum disorders (ASDs) are characterized by core domains: persistent deficits in social communication and interaction; restricted, repetitive patterns of behavior, interests, or activities. ASDs comprise heterogeneous and complex neurodevelopmental pathologies with well-defined inflammatory conditions and immune system dysfunction. Due to neurobiologic changes underlying ASD development, cell-based therapies have been proposed and applied to ASDs. Indeed, stem cells show specific immunologic properties, which make them promising candidates in ASD treatment. This comprehensive up-to-date review focuses on ASD cellular/molecular abnormalities, potentially useful stem cell types, animal models, and current clinical trials on the use of stem cells in treating autism. Limitations are also discussed.
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Affiliation(s)
- Dario Siniscalco
- Department of Experimental Medicine, University of Campania, Napoli, Italy,
| | - Suresh Kannan
- Department of Biomedical Sciences, Sri Ramachandra Institute of Higher Education and Research, Chennai, Tamil Nadu, India
| | - Neomar Semprún-Hernández
- Research Division, Autism Immunology Unit of Maracaibo, Catedra libre de Autismo, Universidad del Zulia, Maracaibo, Venezuela
| | - Adrien A Eshraghi
- Department of Otolaryngology, Hearing Research and Cochlear Implant Laboratory, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | - Nicola Antonucci
- Biomedical Centre for Autism Research and Treatment, Bari, Italy
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29
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Abbaspanah B, Momeni M, Ebrahimi M, Mousavi SH. Advances in perinatal stem cells research: a precious cell source for clinical applications. Regen Med 2018; 13:595-610. [PMID: 30129876 DOI: 10.2217/rme-2018-0019] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2018] [Accepted: 06/08/2018] [Indexed: 12/16/2022] Open
Abstract
Perinatal tissues possess numerous types of stem (stromal) cells, which are considered effective candidates for cell therapy. These tissues possess common characteristics of both embryonic and adult stem cells, and cell therapists have begun to use perinatal stem cells to treat several diseases. Despite their benefits, these cells are considered biological waste and usually discarded after delivery. This review highlights the characteristics and potential clinical applications in regenerative medicine of perinatal stem cell sources - cord blood hematopoietic stem cells, umbilical cord mesenchymal stem cells, amniotic membrane stem cells, amniotic fluid stem cells, amniotic epithelial cells and chorionic mesenchymal stem cells.
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Affiliation(s)
| | - Maryam Momeni
- Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
| | - Marzieh Ebrahimi
- Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
- Department of Stem Cells & Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology & Technology, ACECR, Tehran, Iran
| | - Seyed Hadi Mousavi
- Department of Hematology, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
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30
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Khoury O, Barrios C, Ortega V, Atala A, Murphy SV. Immunomodulatory Cell Therapy to Target Cystic Fibrosis Inflammation. Am J Respir Cell Mol Biol 2018; 58:12-20. [PMID: 28707978 DOI: 10.1165/rcmb.2017-0160tr] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Cystic fibrosis (CF) is associated with exaggerated and prolonged inflammation in the lungs, which contributes to lung injury, airway mucus obstruction, bronchiectasis, and loss of lung function. This hyperinflammatory phenotype appears to be caused by an imbalance between the pro- and antiinflammatory regulatory pathways, with heightened proinflammatory stimuli, a decreased counter-regulatory response, and reduced effectiveness of immune cell function and inflammatory resolution. Thus, therapies that can target this inflammatory environment would have a major impact on preventing the progression of lung disease. Because of the complex phenotype of CF inflammation, current antiinflammatory regimens have proven to be inadequate for the targeting of these multiple dysregulated pathways and effects. Several approaches using cell therapies have shown potential therapeutic benefit for the treatment of CF inflammation. This review provides an overview of the immune dysfunctions in CF and current therapeutic regimens; explores the field of cell therapy as a treatment for CF inflammation; and focuses on the various cell types used, their immunomodulatory functions, and the current approaches to mitigate the inflammatory response and reduce the long-term damage for patients with CF.
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Affiliation(s)
- Oula Khoury
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; and
| | - Christopher Barrios
- 2 Cystic Fibrosis Adult Care Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
| | - Victor Ortega
- 2 Cystic Fibrosis Adult Care Center, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
| | - Anthony Atala
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; and
| | - Sean V Murphy
- 1 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina; and
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31
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Immunomodulatory properties of umbilical cord vein mesenchymal stromal cells influenced by gestational age and in vitro expansion. Immunol Lett 2017; 194:62-68. [PMID: 29175314 DOI: 10.1016/j.imlet.2017.11.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2017] [Revised: 11/20/2017] [Accepted: 11/21/2017] [Indexed: 02/08/2023]
Abstract
In vivo and in vitro aging of the mesenchymal stromal cells (MSCs) can affects their properties. We investigated the immunomodulatory properties of the term and preterm human umbilical cord vein MSCs (UCV-MSCs) at the passages (P) 2 and 5. Term and preterm UCV-MSCs at P2 and 5 were co-cultured with two-way mixed lymphocyte reaction. Proliferation, IFN-γ and IL-10 protein levels, mRNA levels of the COX-2, TGF-β1, TNF-α, IL-4 and FoxP3 were assessed. The term UCV-MSCs and P5 of the term and preterm UCV-MSCs had stronger inhibitory effects on cell proliferation than the preterm UCV-MSC and P2, respectively (P = 0.001). In supernatants of the co-cultures, IFN-γ was higher in the term UCV-MSC than the preterm UCV-MSC, while IL-10 was higher in the preterm UCV-MSCs than the term UCV-MSCs. Also in the co-cultures, COX-2 expression in the term UCV-MSCs and P2 was higher than the preterm UCV-MSCs and P5, respectively and TGF-β1 expression in the term UCV-MSCs was higher than preterm. Conclusively it appears that the term UCV-MSCs, and P5 of the term and preterm UCV-MSCs showed a higher immunomodulatory ability than the preterm UCV-MSCs and P2, respectively.
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32
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Xu J, Sun M, Tan Y, Wang H, Wang H, Li P, Xu Z, Xia Y, Li L, Li Y. Effect of matrix stiffness on the proliferation and differentiation of umbilical cord mesenchymal stem cells. Differentiation 2017; 96:30-39. [PMID: 28753444 DOI: 10.1016/j.diff.2017.07.001] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2017] [Revised: 07/09/2017] [Accepted: 07/18/2017] [Indexed: 12/18/2022]
Abstract
Mesenchymal stem cells (MSCs) are a compatible cellular alternative for regenerative medicine and tissue engineering because of their powerful multipotency. Matrix stiffness plays a profound role on stem cell behavior. Nevertheless, the effect of matrix stiffness on umbilical cordmesenchymal stem cells (UC-MSCs) remains unexplored. To conduct an in-depth exploration, we cultured UC-MSCs on different stiffness (Young's modulus: 13-16, 35-38, 48-53, and 62-68 kPa) polyacrylamide gels coated with fibronectin. We found that the proliferation and adhesion of UC-MSCs varied when cultured on the different matrices, and the spreading capacity was stronger as the stiffness increased (*P<0.05). Real-time quantitative PCR results showed that the soft matrix promoted adipogenic differentiation, with higher expression levels of adipocytic markers like PPARγ and C/EBPα (*P<0.05). In contrast, cells tended to differentiate into muscle when cultured on the 48-53 kPa matrix, which was validated by increased expression of myogenic makers like desminand MOYG (*P<0.05). Moreover, increased expression of osteoblastic makers (*P<0.05), such as ALP, collagen type I, osteocalcin, and Runx2, confirmed that cells differentiated into bone on the high-stiffness matrix.
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Affiliation(s)
- Juanjuan Xu
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Meiyu Sun
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Ye Tan
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Haowei Wang
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Heping Wang
- Department of Neurosurgery, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, Wuhan, China
| | - Pengdong Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Ziran Xu
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Yuhan Xia
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China
| | - Lisha Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China.
| | - Yulin Li
- The Key Laboratory of Pathobiology, Ministry of Education, Norman Bethune Medical College, Jilin University, Changchun, China.
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Pu L, Meng M, Wu J, Zhang J, Hou Z, Gao H, Xu H, Liu B, Tang W, Jiang L, Li Y. Compared to the amniotic membrane, Wharton's jelly may be a more suitable source of mesenchymal stem cells for cardiovascular tissue engineering and clinical regeneration. Stem Cell Res Ther 2017; 8:72. [PMID: 28320452 PMCID: PMC5359832 DOI: 10.1186/s13287-017-0501-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 01/23/2017] [Accepted: 02/09/2017] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND The success of developing cardiovascular tissue engineering (CTE) grafts greatly needs a readily available cell substitute for endothelial and interstitial cells. Perinatal annexes have been proposed as a valuable source of mesenchymal stem cells (MSCs) for tissue engineering and regenerative medicine. The objective of the present study is to evaluate the potential of human Wharton's jelly MSCs (WJ-MSCs) and amniotic membrane MSCs (AM-MSCs) as a seeding cell in CTE and cardiovascular regenerative medicine. METHODS WJ-MSCs/AM-MSCs were isolated and characterized in vitro according to their morphology, proliferation, self-renewal, phenotype, and multipotency. More importantly, the characteristics of hemocompatibility, extracellular matrix deposition, and gene expression and viability of both MSCs were investigated. RESULTS Fibroblast-like human WJ-MSCs and AM-MSCs were successfully isolated and positively expressed the characteristic markers CD73, CD90, and CD105 but were negative for CD34, CD45, and HLA-DR. Both MSCs shared trilineage differentiation toward the adipogenic, osteogenic, and chondrogenic lineages. The proliferative and self-renewal capacity of WJ-MSCs was significantly higher than that of AM-MSCs (P < 0.001). WJ-MSCs provided comparable properties of antiplatelet adhesion and did not activate the coagulation cascade to endothelial cells. However, aggregated platelets were visualized on the surface of AM-MSCs-derived cell sheets and the intrinsic pathway was activated. Furthermore, WJ-MSCs have superior properties of collagen deposition and higher viability than AM-MSCs during cell sheet formation. CONCLUSIONS This study highlights that WJ-MSCs could act as a functional substitute of endothelial and interstitial cells, which could serve as an appealing and practical single-cell source for CTE and regenerative therapy.
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Affiliation(s)
- Lei Pu
- Department of Cardiovascular Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Mingyao Meng
- Central Laboratory, Yan’an Affiliated Hospital of Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Jian Wu
- Department of Cardiovascular Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
- Cardiovascular Surgery Institute of Yunnan, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Jing Zhang
- Department of Anesthesiology, The Second Affiliated Hospital of Kunming Medical University, 374, Dianmian Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Zongliu Hou
- Central Laboratory, Yan’an Affiliated Hospital of Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Hui Gao
- Central Laboratory, Yan’an Affiliated Hospital of Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Hui Xu
- Department of Thoracic Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Boyu Liu
- Department of Cardiovascular Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Weiwei Tang
- Central Laboratory, Yan’an Affiliated Hospital of Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
| | - Lihong Jiang
- Department of Cardiovascular Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
- Cardiovascular Surgery Institute of Yunnan, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
- First People’s Hospital of Yunnan Province, 157, Jinbi Road, Kunming, Yunnan People’s Republic of China
| | - Yaxiong Li
- Department of Cardiovascular Surgery, Yan’an Affiliated Hospital of Kunming Medical University, Kunming Medical University, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
- Cardiovascular Surgery Institute of Yunnan, 245, East of Renmin Road, Kunming, 650051 Yunnan People’s Republic of China
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Lee S, Park BJ, Kim JY, Jekarl D, Choi HY, Lee SY, Kim M, Kim Y, Park MS. The effect of fibroblast growth factor on distinct differentiation potential of cord blood-derived unrestricted somatic stem cells and Wharton's jelly-derived mesenchymal stem/stromal cells. Cytotherapy 2016; 17:1723-31. [PMID: 26589753 DOI: 10.1016/j.jcyt.2015.09.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Revised: 09/08/2015] [Accepted: 09/18/2015] [Indexed: 01/27/2023]
Abstract
BACKGROUND AIMS Perinatal tissues are considered an attractive source of mesenchymal stem/stromal cells (MSCs) and have unique characteristics depending on their origin. In this study, we compared the basic characteristics of unrestricted somatic stem cells isolated from cord blood (CB-USSCs) and MSCs isolated from Wharton's jelly of umbilical cords (WJ-MSCs). We also evaluated the effect of basic fibroblast growth factor (bFGF) supplementation on the growth and differentiation of these cells. METHODS CB-USSCs and WJ-MSCs were isolated from the same individual (n = 6), and their morphology, cell surface antigens, proliferation, expression of stemness markers and adipogenic, osteogenic and chondrogenic differentiation potentials were evaluated. Their morphology, proliferation and differentiation potentials were then also compared in the presence of bFGF supplementation (10 ng/mL). RESULTS Overall, CB-USSCs expressed DLK-1 and negative for all the HOX gene markers. The expression of cell surface antigen CD90, growth capacity and adipogenic differential potential of CB-USSCs were lower than those of WJ-MSCs. WJ-MSCs showed higher growth capacity, but the expression of CD73 and CD105 and their osteogenic differentiation potential were lower than those of CB-USSCs. The spindle morphology of both CB-USSCs and WJ-MSCs and the growth and adipogenic differentiation of CB-USSCs were improved by bFGF supplementation. However, the bFGF supplement did not have any positive effect on the tri-lineage differentiation potentials of WJ-MSCs. CONCLUSIONS CB-USSCs and WJ-MSCs each had distinct characteristics including different growth capacity, distinguishable cell surface markers and distinct adipogenic and osteogenic potentials. bFGF supplementation improved the growth capacity and adipogenic differentiation of CB-USSCs.
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Affiliation(s)
- Seungok Lee
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea; Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Byung-Joon Park
- Department of Obstetrics and Gynecology, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Ji Yeon Kim
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - DongWook Jekarl
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea; Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Hyun Yoo Choi
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Seong Yeoun Lee
- Department of Laboratory Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
| | - Myungshin Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
| | - Yonggoo Kim
- Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Moon-Seo Park
- Institute of Catholic Integrative Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, South Korea
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Somal A, Bhat IA, B. I, Pandey S, Panda BSK, Thakur N, Sarkar M, Chandra V, Saikumar G, Sharma GT. A Comparative Study of Growth Kinetics, In Vitro Differentiation Potential and Molecular Characterization of Fetal Adnexa Derived Caprine Mesenchymal Stem Cells. PLoS One 2016; 11:e0156821. [PMID: 27257959 PMCID: PMC4892572 DOI: 10.1371/journal.pone.0156821] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Accepted: 05/02/2016] [Indexed: 02/07/2023] Open
Abstract
The present study was conducted with an objective of isolation, in vitro expansion, growth kinetics, molecular characterization and in vitro differentiation of fetal adnexa derived caprine mesenchymal stem cells. Mid-gestation gravid caprine uteri (2–3 months) were collected from abattoir to derive mesenchymal stem cells (MSCs) from fetal adnexa {amniotic fluid (cAF), amniotic sac (cAS), Wharton’s jelly (cWJ) and cord blood (cCB)} and expanded in vitro. These cultured MSCs were used at the 3rd passage (P3) to study growth kinetics, localization as well as molecular expression of specific surface antigens, pluripotency markers and mesenchymal tri-lineage differentiation. In comparison to cAF and cAS MSCs, cWJ and cCB MSCs showed significantly (P<0.05) higher clonogenic potency, faster growth rate and low population doubling (PDT) time. All the four types of MSCs were positive for alkaline phosphatase (AP) and differentiated into chondrogenic, osteogenic, and adipogenic lineages. These stem cells expressed MSC surface antigens (CD73, CD90 and CD105) and pluripotency markers (Oct4, Sox2, Nanog, KLF, cMyc, FoxD3) but did not express CD34, a hematopoietic stem cell marker (HSC) as confirmed by RT-PCR, immunocytochemistry and flow cytometric analysis. The relative mRNA expression of MSC surface antigens (CD73, CD90 and CD105) was significantly (P<0.05) higher in cWJ MSCs compared to the other cell lines. The mRNA expression of Oct4 was significantly (P<0.05) higher in cWJ, whereas mRNA expression of KLF and cMyc was significantly (P<0.05) higher in cWJ and cAF than that of cAS and cCB. The comparative assessment revealed that cWJ MSCs outperformed MSCs from other sources of fetal adnexa in terms of growth kinetics, relative mRNA expression of surface antigens, pluripotency markers and tri-lineage differentiation potential, hence, these MSCs could be used as a preferred source for regenerative medicine.
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Affiliation(s)
- Anjali Somal
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Irfan A. Bhat
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Indu B.
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Sriti Pandey
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Bibhudatta S. K. Panda
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Nipuna Thakur
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Mihir Sarkar
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - Vikash Chandra
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - G. Saikumar
- Division of Veterinary Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
| | - G. Taru Sharma
- Division of Physiology and Climatology, ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, Bareilly, U.P., India
- * E-mail:
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Mandò C, Razini P, Novielli C, Anelli GM, Belicchi M, Erratico S, Banfi S, Meregalli M, Tavelli A, Baccarin M, Rolfo A, Motta S, Torrente Y, Cetin I. Impaired Angiogenic Potential of Human Placental Mesenchymal Stromal Cells in Intrauterine Growth Restriction. Stem Cells Transl Med 2016; 5:451-63. [PMID: 26956210 DOI: 10.5966/sctm.2015-0155] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 12/21/2015] [Indexed: 01/12/2023] Open
Abstract
UNLABELLED Human placental mesenchymal stromal cells (pMSCs) have never been investigated in intrauterine growth restriction (IUGR). We characterized cells isolated from placental membranes and the basal disc of six IUGR and five physiological placentas. Cell viability and proliferation were assessed every 7 days during a 6-week culture. Expression of hematopoietic, stem, endothelial, and mesenchymal markers was evaluated by flow cytometry. We characterized the multipotency of pMSCs and the expression of genes involved in mitochondrial content and function. Cell viability was high in all samples, and proliferation rate was lower in IUGR compared with control cells. All samples presented a starting heterogeneous population, shifting during culture toward homogeneity for mesenchymal markers and occurring earlier in IUGR than in controls. In vitro multipotency of IUGR-derived pMSCs was restricted because their capacity for adipocyte differentiation was increased, whereas their ability to differentiate toward endothelial cell lineage was decreased. Mitochondrial content and function were higher in IUGR pMSCs than controls, possibly indicating a shift from anaerobic to aerobic metabolism, with the loss of the metabolic characteristics that are typical of undifferentiated multipotent cells. SIGNIFICANCE This study demonstrates that the loss of endothelial differentiation potential and the increase of adipogenic ability are likely to play a significant role in the vicious cycle of abnormal placental development in intrauterine growth restriction (IUGR). This is the first observation of a potential role for placental mesenchymal stromal cells in intrauterine growth restriction, thus leading to new perspectives for the treatment of IUGR.
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Affiliation(s)
- Chiara Mandò
- "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy
| | - Paola Razini
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy
| | - Chiara Novielli
- "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy
| | - Gaia Maria Anelli
- "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy
| | - Marzia Belicchi
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy
| | | | - Stefania Banfi
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy
| | - Mirella Meregalli
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy
| | - Alessandro Tavelli
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy
| | - Marco Baccarin
- Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Alessandro Rolfo
- Department of Surgical Science, University of Turin, Turin, Italy
| | - Silvia Motta
- Laboratory of Medical Genetics, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Yvan Torrente
- Stem Cell Laboratory, Department of Pathophysiology and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, Universitá degli Studi di Milano, Milan, Italy Ystem S.R.L., Milan, Italy UNISTEM Interdepartmental Centre for Stem Cell Research, Milan, Italy
| | - Irene Cetin
- "L. Sacco" Department of Biomedical and Clinical Sciences, Center for Fetal Research Giorgio Pardi, Universitá degli Studi di Milano, Milan, Italy Department of Mother and Child, Luigi Sacco Hospital, Milan, Italy
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Rammal H, Harmouch C, Lataillade JJ, Laurent-Maquin D, Labrude P, Menu P, Kerdjoudj H. Stem cells: a promising source for vascular regenerative medicine. Stem Cells Dev 2015; 23:2931-49. [PMID: 25167472 DOI: 10.1089/scd.2014.0132] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
The rising and diversity of many human vascular diseases pose urgent needs for the development of novel therapeutics. Stem cell therapy represents a challenge in the medicine of the twenty-first century, an area where tissue engineering and regenerative medicine gather to provide promising treatments for a wide variety of diseases. Indeed, with their extensive regeneration potential and functional multilineage differentiation capacity, stem cells are now highlighted as promising cell sources for regenerative medicine. Their multilineage differentiation involves environmental factors such as biochemical, extracellular matrix coating, oxygen tension, and mechanical forces. In this review, we will focus on human stem cell sources and their applications in vascular regeneration. We will also discuss the different strategies used for their differentiation into both mature and functional smooth muscle and endothelial cells.
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Affiliation(s)
- Hassan Rammal
- 1 UMR 7365, Biopôle, Faculté de Médecine, CNRS-Université de Lorraine , Vandœuvre-lès-Nancy, France
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Li J, He F, Pei M. Chondrogenic priming of human fetal synovium-derived stem cells in an adult stem cell matrix microenvironment. Genes Dis 2015; 2:337-346. [PMID: 30258873 PMCID: PMC6147170 DOI: 10.1016/j.gendis.2015.06.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2015] [Accepted: 06/29/2015] [Indexed: 02/08/2023] Open
Abstract
Cartilage defects are a challenge to treat clinically due to the avascular nature of cartilage. Low immunogenicity and extensive proliferation and multidifferentiation potential make fetal stem cells a promising source for regenerative medicine. In this study, we aimed to determine whether fetal synovium-derived stem cells (FSDSCs) exhibited replicative senescence and whether expansion on decellularized extracellular matrix (dECM) deposited by adult SDSCs (AECM) promoted FSDSCs' chondrogenic potential. FSDSCs from passage 2 and 9 were compared for chondrogenic potential, using Alcian blue staining for sulfated glycosaminoglycans (GAGs), biochemical analysis for DNA and GAG amounts, and real-time PCR for chondrogenic genes including ACAN and COL2A1. Passage 3 FSDSCs were expanded for one passage on plastic flasks (PL), AECM, or dECM deposited by fetal SDSCs (FECM). During expansion, cell proliferation was evaluated using flow cytometry for proliferation index, stem cell surface markers, and resistance to hydrogen peroxide. During chondrogenic induction, expanded FSDSCs were evaluated for tri-lineage differentiation capacity. We found that cell expansion enhanced FSDSCs' chondrogenic potential at least up to passage 9. Expansion on dECMs promoted FSDSCs' proliferative and survival capacity and adipogenic differentiation but not osteogenic capacity. AECM-primed FSDSCs exhibited an enhanced chondrogenic potential.
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Affiliation(s)
- Jingting Li
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA.,Division of Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA
| | - Fan He
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA.,Division of Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA.,Orthopaedic Institute, Soochow University, Suzhou 215007, China
| | - Ming Pei
- Stem Cell and Tissue Engineering Laboratory, Department of Orthopaedics, West Virginia University, Morgantown, WV 26506, USA.,Division of Exercise Physiology, West Virginia University, Morgantown, WV 26506, USA
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Si JW, Wang XD, Shen SGF. Perinatal stem cells: A promising cell resource for tissue engineering of craniofacial bone. World J Stem Cells 2015; 7:149-159. [PMID: 25621114 PMCID: PMC4300925 DOI: 10.4252/wjsc.v7.i1.149] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 08/28/2014] [Accepted: 09/17/2014] [Indexed: 02/06/2023] Open
Abstract
In facing the mounting clinical challenge and suboptimal techniques of craniofacial bone defects resulting from various conditions, such as congenital malformations, osteomyelitis, trauma and tumor resection, the ongoing research of regenerative medicine using stem cells and concurrent advancement in biotechnology have shifted the focus from surgical reconstruction to a novel stem cell-based tissue engineering strategy for customized and functional craniofacial bone regeneration. Given the unique ontogenetical and cell biological properties of perinatal stem cells, emerging evidence has suggested these extraembryonic tissue-derived stem cells to be a promising cell source for extensive use in regenerative medicine and tissue engineering. In this review, we summarize the current achievements and obstacles in stem cell-based craniofacial bone regeneration and subsequently we address the characteristics of various types of perinatal stem cells and their novel application in tissue engineering of craniofacial bone. We propose the promising feasibility and scope of perinatal stem cell-based craniofacial bone tissue engineering for future clinical application.
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Embryonic stem cells conditioned medium enhances Wharton's jelly-derived mesenchymal stem cells expansion under hypoxic condition. Cytotechnology 2014; 67:493-505. [PMID: 25326788 DOI: 10.1007/s10616-014-9708-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2013] [Accepted: 02/19/2014] [Indexed: 12/22/2022] Open
Abstract
Mesenchymal stem cells (MSCs) are accepted as a promising tool for therapeutic purposes. However, low proliferation and early senescence are still main obstacles of MSCs expansion for using as cell-based therapy. Thus, clinical scale of cell expansion is needed to obtain a large number of cells serving for further applications. In this study, we investigated the value of embryonic stem cells conditioned medium (ESCM) for in vitro expansion of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) as compared to typical culture medium for MSCs, Dulbecco's modified Eagle's medium with 1.0 g/l glucose (DMEM-LG) supplemented with 10 % FBS, under hypoxic condition. The expanded cells from ESCM (ESCM-MSCs) and DMEM-LG (DMEM-MSCs) were characterized for both phenotype and biological activities including proliferation rate, population doubling time, cell cycle distribution and MSCs characteristics. ESCM and DMEM-LG could enhance WJ-MSCs proliferation as 204.66 ± 10.39 and 113.77 ± 7.89 fold increase at day 12, respectively. ESCM-MSCs could express pluripotency genes including Oct-4, Oct-3/4, Nanog, Klf-4, C-Myc and Sox-2 both in early and late passages whereas the downregulations of Oct-4 and Nanog were detected in late passage cells of DMEM-MSCs. The 2 cell populations also showed common MSCs characteristics including normal cell cycle, fibroblastic morphology, cell surface markers expressions (CD29(+), CD44(+), CD90(+), CD34(-), CD45(-)) and differentiation capacities into adipogenic, chondrogenic and osteogenic lineages. Moreover, our results revealed that ESCM exhibited as a rich source of several factors which are required for supportive WJ-MSCs proliferation. In conclusion, ESCM under hypoxic condition could accelerate WJ-MSCs expansion while maintaining their pluripotency properties. Our knowledge provide short term and cost-saving in WJ-MSCs expansion which has benefit to overcome insufficient cell numbers for clinical applications by reusing the discarded cell culture supernates from human ES culture system. Moreover, these findings can also apply for stem cell banking, regenerative medicine and pharmacological applications.
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Taran R, Mamidi MK, Singh G, Dutta S, Parhar IS, John JP, Bhonde R, Pal R, Das AK. In vitro and in vivo neurogenic potential of mesenchymal stem cells isolated from different sources. J Biosci 2014; 39:157-69. [PMID: 24499800 DOI: 10.1007/s12038-013-9409-5] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Regenerative medicine is an evolving interdisciplinary topic of research involving numerous technological methods that utilize stem cells to repair damaged tissues. Particularly, mesenchymal stem cells (MSCs) are a great tool in regenerative medicine because of their lack of tumorogenicity, immunogenicity and ability to perform immunomodulatory as well as anti-inflammatory functions. Numerous studies have investigated the role of MSCs in tissue repair and modulation of allogeneic immune responses. MSCs derived from different sources hold unique regenerative potential as they are self-renewing and can differentiate into chondrocytes, osteoblasts, adipocytes, cardiomyocytes, hepatocytes, endothelial and neuronal cells, among which neuronal-like cells have gained special interest. MSCs also have the ability to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation. In this review we focus on neural differentiation potential of MSCs isolated from different sources and how certain growth factors/small molecules can be used to derive neuronal phenotypes from MSCs. We also discuss the efficacy of MSCs when transplanted in vivo and how they can generate certain neurons and lead to relief or recovery of the diseased condition. Furthermore, we have tried to evaluate the appropriatemerits of different sources ofMSCs with respect to their propensity towards neurological differentiation as well as their effectiveness in preclinical studies.
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Affiliation(s)
- Ramyani Taran
- Manipal Institute of Regenerative Medicine, Manipal University Branch Campus, Bangalore, India
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Constantinescu A, Andrei E, Iordache F, Constantinescu E, Maniu H. Recellularization potential assessment of Wharton's Jelly-derived endothelial progenitor cells using a human fetal vascular tissue model. In Vitro Cell Dev Biol Anim 2014; 50:937-44. [PMID: 25124869 DOI: 10.1007/s11626-014-9797-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Accepted: 07/07/2014] [Indexed: 12/27/2022]
Abstract
Mesenchymal stem cells isolated from Wharton's Jelly have demonstrated an excellent differentiation potential into the endothelial lineage. We hypothesize that endothelial progenitor cells differentiated from Wharton's Jelly-derived mesenchymal stem cells have the potential to repopulate a decellularized vascular bed employed as a biological scaffold. For this purpose, we aimed at investigating the behavior of the endothelial progenitor cells in the decellularized matrix and their potential to repopulate decellularized human vascular tissue. Our main objectives were to differentiate Wharton's Jelly-derived mesenchymal stem cells into endothelial progenitor cells and to obtain a human vascular tissue slice experimental model using the umbilical cord arteries. We employed a decellularization method using enzymatic treatment of the umbilical cord arteries and a recellularization method with the endothelial progenitor cells differentiated from Wharton's Jelly mesenchymal cells in a co-culture system, in order to investigate our hypothesis. The cellular integration within the biological scaffold was determined by using flow cytometry analysis and confirmed by visualization of histological staining as well as fluorescence microscopy. The morphological observations of the recellularized scaffolds revealed the presence of endothelial progenitor cells within the decellularized tissue slices, displaying no degradation of the scaffold's extracellular matrix. The flow cytometry analysis revealed the presence of Wharton's Jelly-derived endothelial progenitor cells population in the decellularized fetal blood vessel scaffold after recellularization. In conclusion, our results have shown that an in vitro human vascular tissue slice experimental model using decellularized human fetal arteries is able to sustain an adequate scaffold for cellular implants.
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Affiliation(s)
- Andrei Constantinescu
- Institute of Cellular Biology and Pathology "Nicole Simionescu" of the Romanian Academy, 050568, Bucharest, Romania
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Filioli Uranio M, Dell'Aquila ME, Caira M, Guaricci AC, Ventura M, Catacchio CR, Martino NA, Valentini L. Characterization and in vitro differentiation potency of early-passage canine amnion- and umbilical cord-derived mesenchymal stem cells as related to gestational age. Mol Reprod Dev 2014; 81:539-51. [PMID: 24659564 DOI: 10.1002/mrd.22322] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 03/15/2014] [Indexed: 12/20/2022]
Abstract
Fetal adnexa are a non-controversial source of mesenchymal stem cells (MSCs) that have high plasticity, a high proliferation rate, and the ability to differentiate towards multiple lineages. MSC populations have been characterized for their stemness and differentiation capabilities; more recent work has focused on MSC selection and on establishing predictable elements to discriminate the cells with the most potential for regenerative medicine. In this study, we cytogenetically and molecularly characterized and followed the in vitro proliferation and differentiation potential of early-passage canine amniotic membrane MSCs (AM-MSCs) and umbilical cord matrix MSCs (UCM-MSCs) isolated from fetuses at early (35-40 days) and late (45-55 days) gestational ages. We found that cells from both fetal gestational ages showed similar features. In all examined cell lines, the morphology of proliferating cells typically appeared fibroblast-like. Population doublings, passaged up to 10 times, increased significantly with passage number. In both cell types, cell viability and chromosomal number and structure were not affected by gestational age at early passages. Passage-3 AM- and UCM-MSCs from both gestational phases also expressed embryonic (POU5F1) and mesenchymal (CD29, CD44) stemness markers, whereas hematopoietic and histocompatibility markers were never found in any sample. Passage-3 cell populations of each cell type were also multipotential as they could differentiate into neurocytes and osteocytes, based on cell morphology, specific stains, and molecular analysis. These results indicated that MSCs retrieved from the UCM and AM in the early and late fetal phases of gestation could be used for canine regenerative medicine.
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Affiliation(s)
- Manuel Filioli Uranio
- Veterinary Clinics and Animal Productions Section, Department for Emergency and Organ Transplantation, University of Bari Aldo Moro, Valenzano, Italy
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Faghihi F, Baghaban Eslaminejad M. The effect of nano-scale topography on osteogenic differentiation of mesenchymal stem cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158:5-16. [DOI: 10.5507/bp.2013.013] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2012] [Accepted: 02/14/2013] [Indexed: 01/08/2023] Open
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Indumathi S, Harikrishnan R, Mishra R, Rajkumar J, Padmapriya V, Lissa R, Dhanasekaran M. Comparison of feto-maternal organ derived stem cells in facets of immunophenotype, proliferation and differentiation. Tissue Cell 2013; 45:434-42. [DOI: 10.1016/j.tice.2013.07.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2012] [Revised: 07/28/2013] [Accepted: 07/29/2013] [Indexed: 10/26/2022]
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Abstract
Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. ASDs are clinically defined by deficits in communication, social skills, and repetitive and/or restrictive interests and behaviours. With the prevalence rates for ASDs rapidly increasing, the need for effective therapies for autism is a priority for biomedical research. Currently available medications do not target the core symptoms, can have markedly adverse side-effects, and are mainly palliative for negative behaviours. The development of molecular and regenerative interventions is progressing rapidly, and medicine holds great expectations for stem cell therapies. Cells could be designed to target the observed molecular mechanisms of ASDs, that is, abnormal neurotransmitter regulation, activated microglia, mitochondrial dysfunction, blood-brain barrier disruptions, and chronic intestinal inflammation. Presently, the paracrine, secretome, and immunomodulatory effects of stem cells would appear to be the likely mechanisms of application for ASD therapeutics. This review will focus on the potential use of the various types of stem cells: embryonic, induced pluripotential, fetal, and adult stem cells as targets for ASD therapeutics.
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Perspectives on the use of stem cells for autism treatment. Stem Cells Int 2013; 2013:262438. [PMID: 24222772 PMCID: PMC3810518 DOI: 10.1155/2013/262438] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2013] [Revised: 08/22/2013] [Accepted: 09/06/2013] [Indexed: 12/13/2022] Open
Abstract
Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. ASDs are clinically defined by deficits in communication, social skills, and repetitive and/or restrictive interests and behaviours. With the prevalence rates for ASDs rapidly increasing, the need for effective therapies for autism is a priority for biomedical research. Currently available medications do not target the core symptoms, can have markedly adverse side-effects, and are mainly palliative for negative behaviours. The development of molecular and regenerative interventions is progressing rapidly, and medicine holds great expectations for stem cell therapies. Cells could be designed to target the observed molecular mechanisms of ASDs, that is, abnormal neurotransmitter regulation, activated microglia, mitochondrial dysfunction, blood-brain barrier disruptions, and chronic intestinal inflammation. Presently, the paracrine, secretome, and immunomodulatory effects of stem cells would appear to be the likely mechanisms of application for ASD therapeutics. This review will focus on the potential use of the various types of stem cells: embryonic, induced pluripotential, fetal, and adult stem cells as targets for ASD therapeutics.
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48
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Eckert MA, Vu Q, Xie K, Yu J, Liao W, Cramer SC, Zhao W. Evidence for high translational potential of mesenchymal stromal cell therapy to improve recovery from ischemic stroke. J Cereb Blood Flow Metab 2013; 33:1322-34. [PMID: 23756689 PMCID: PMC3764389 DOI: 10.1038/jcbfm.2013.91] [Citation(s) in RCA: 103] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2013] [Revised: 05/06/2013] [Accepted: 05/08/2013] [Indexed: 12/27/2022]
Abstract
Although ischemic stroke is a major cause of morbidity and mortality, current therapies benefit only a small proportion of patients. Transplantation of mesenchymal stromal cells (MSC, also known as mesenchymal stem cells or multipotent stromal cells) has attracted attention as a regenerative therapy for numerous diseases, including stroke. Mesenchymal stromal cells may aid in reducing the long-term impact of stroke via multiple mechanisms that include induction of angiogenesis, promotion of neurogenesis, prevention of apoptosis, and immunomodulation. In this review, we discuss the clinical rationale of MSC for stroke therapy in the context of their emerging utility in other diseases, and their recent clinical approval for treatment of graft-versus-host disease. An analysis of preclinical studies examining the effects of MSC therapy after ischemic stroke indicates near-universal agreement that MSC have significant favorable effect on stroke recovery, across a range of doses and treatment time windows. These results are interpreted in the context of completed and ongoing human clinical trials, which provide support for MSC as a safe and potentially efficacious therapy for stroke recovery in humans. Finally, we consider principles of brain repair and manufacturing considerations that will be useful for effective translation of MSC from the bench to the bedside for stroke recovery.
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Affiliation(s)
- Mark A Eckert
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
| | - Quynh Vu
- Department of Neurology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Kate Xie
- Department of Neurology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Jingxia Yu
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
| | - Wenbin Liao
- Department of Pathology, State University of New York at Stony Brook, Stony Brook, New York, USA
| | - Steven C Cramer
- Departments of Neurology and Anatomy and Neurobiology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, California, USA
| | - Weian Zhao
- Departments of Pharmaceutical Sciences and Biomedical Engineering, Sue and Bill Gross Stem Cell Research Center, Chao Family Comprehensive Cancer Center, University of California, Irvine, California, USA
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Cellular kinetics of perivascular MSC precursors. Stem Cells Int 2013; 2013:983059. [PMID: 24023546 PMCID: PMC3760099 DOI: 10.1155/2013/983059] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2013] [Accepted: 07/13/2013] [Indexed: 12/26/2022] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.
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50
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Garzón I, Miyake J, González-Andrades M, Carmona R, Carda C, Sánchez-Quevedo MDC, Campos A, Alaminos M. Wharton's jelly stem cells: a novel cell source for oral mucosa and skin epithelia regeneration. Stem Cells Transl Med 2013; 2:625-32. [PMID: 23817131 DOI: 10.5966/sctm.2012-0157] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Perinatal stem cells such as human umbilical cord Wharton's jelly stem cells (HWJSCs) are excellent candidates for tissue engineering because of their proliferation and differentiation capabilities. However, their differentiation potential into epithelial cells at in vitro and in vivo levels has not yet been reported. In this work we have studied the capability of HWJSCs to differentiate in vitro and in vivo to oral mucosa and skin epithelial cells using a bioactive three-dimensional model that mimics the native epithelial-mesenchymal interaction. To achieve this, primary cell cultures of HWJSCs, oral mucosa, and skin fibroblasts were obtained in order to generate a three-dimensional heterotypical model of artificial oral mucosa and skin based on fibrin-agarose biomaterials. Our results showed that the cells were unable to fully differentiate to epithelial cells in vitro. Nevertheless, in vivo grafting of the bioactive three-dimensional models demonstrated that HWJSCs were able to stratify and to express typical markers of epithelial differentiation, such as cytokeratins 1, 4, 8, and 13, plakoglobin, filaggrin, and involucrin, showing specific surface patterns. Electron microscopy analysis confirmed the presence of epithelial cell-like layers and well-formed cell-cell junctions. These results suggest that HWJSCs have the potential to differentiate to oral mucosa and skin epithelial cells in vivo and could be an appropriate novel cell source for the development of human oral mucosa and skin in tissue engineering protocols.
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Affiliation(s)
- Ingrid Garzón
- Department of Histology (Tissue Engineering Group), University of Granada, Granada, Spain
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