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1
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Wang JJ, Zheng Y, Li YL, Xiao Y, Ren YY, Tian YQ. Emerging role of mesenchymal stem cell-derived exosomes in the repair of acute kidney injury. World J Stem Cells 2025; 17:103360. [PMID: 40160687 PMCID: PMC11947899 DOI: 10.4252/wjsc.v17.i3.103360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 12/26/2024] [Accepted: 02/13/2025] [Indexed: 03/21/2025] Open
Abstract
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid deterioration in kidney function and has a significant impact on patient health and survival. Mesenchymal stem cells (MSCs) have the potential to enhance renal function by suppressing the expression of cell cycle inhibitors and reducing the expression of senescence markers and microRNAs via paracrine and endocrine mechanisms. MSC-derived exosomes can alleviate AKI symptoms by regulating DNA damage, apoptosis, and other related signaling pathways through the delivery of proteins, microRNAs, long-chain noncoding RNAs, and circular RNAs. This technique is both safe and effective. MSC-derived exosomes may have great application prospects in the treatment of AKI. Understanding the underlying mechanisms will foster the development of new and promising therapeutic strategies against AKI. This review focused on recent advancements in the role of MSCs in AKI repair as well as the mechanisms underlying the role of MSCs and their secreted exosomes. It is anticipated that novel and profound insights into the functionality of MSCs and their derived exosomes will emerge.
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Affiliation(s)
- Juan-Juan Wang
- Clinical Laboratory, The First People's Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yu Zheng
- Clinical Laboratory, The First People's Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yan-Lin Li
- Clinical Laboratory, The First People's Hospital of Yancheng, Yancheng First Hospital, Affiliated Hospital of Nanjing University Medical School, Yancheng 224000, Jiangsu Province, China
| | - Yin Xiao
- Department of Medical Imaging, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu Province, China
| | - Yang-Yang Ren
- Clinical Laboratory, Xinyi People's Hospital, Xuzhou 221000, Jiangsu Province, China
| | - Yi-Qing Tian
- Clinical Laboratory, Xuzhou Central Hospital, Xuzhou 221000, Jiangsu Province, China.
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2
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Canciani B, Rossi N, Arrigoni E, Giorgino R, Sergio M, Aidos L, Di Giancamillo M, Herrera Millar VR, Peretti GM, Di Giancamillo A, Mangiavini L. In Vitro Characterization of Human Cell Sources in Collagen Type I Gel Scaffold for Meniscus Tissue Engineering. Gels 2024; 10:767. [PMID: 39727525 DOI: 10.3390/gels10120767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 11/17/2024] [Accepted: 11/19/2024] [Indexed: 12/28/2024] Open
Abstract
Strategies to repair the meniscus have achieved limited success; thus, a cell-based therapy combined with an appropriate biocompatible scaffold could be an interesting alternative to overcome this issue. The aim of this project is to analyze different cell populations and a collagen gel scaffold as a potential source for meniscus tissue engineering applications. Dermal fibroblasts (DFs) and mesenchymal stem cells (MSCs) isolated from adipose tissue (ASCs) or bone marrow (BMSCs) were analyzed. Two different fibro-chondrogenic media, M1 and M2, were tested, and qualitative and quantitative analyses were performed. Significant increases in glycosaminoglycans (GAGs) production and in fibro-cartilaginous marker expression were observed in MSCs in the presence of M1 medium. In addition, both ASCs and BMSCs cultured in M1 medium were used in association with the collagen hydrogel (MSCs-SCF) for the development of an in vitro meniscal-like tissue. Significant up-regulation in GAGs production and in the expression of aggrecan, collagen type I, and collagen type II was observed in BMSCs-SCF. This study improves knowledge of the potential of combining undifferentiated MSCs with a collagen gel as a new tissue engineering strategy for meniscus repair.
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Affiliation(s)
| | - Nicolò Rossi
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, 20157 Milan, Italy
| | - Elena Arrigoni
- Department of Biomedical Sciences for Health, University of Milan, 20141 Milan, Italy
| | - Riccardo Giorgino
- Residency Program in Orthopedics and Traumatology, University of Milan, 20141 Milan, Italy
| | - Mirko Sergio
- Department of Veterinary Medicine and Animal Science, University of Milan, 26900 Lodi, Italy
| | - Lucia Aidos
- Department of Veterinary Medicine and Animal Science, University of Milan, 26900 Lodi, Italy
| | - Mauro Di Giancamillo
- Department of Veterinary Medicine and Animal Science, University of Milan, 26900 Lodi, Italy
| | | | - Giuseppe M Peretti
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, 20157 Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, 20141 Milan, Italy
| | | | - Laura Mangiavini
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, 20157 Milan, Italy
- Department of Biomedical Sciences for Health, University of Milan, 20141 Milan, Italy
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3
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Gallardo J, Berríos-Cárcamo P, Ezquer F. Mesenchymal stem cells as a promising therapy for alcohol use disorder. INTERNATIONAL REVIEW OF NEUROBIOLOGY 2024; 178:179-211. [PMID: 39523054 DOI: 10.1016/bs.irn.2024.07.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Alcohol Use Disorder (AUD) is a highly prevalent medical condition characterized by impaired control over alcohol consumption, despite negative consequences on the individual's daily life and health. There is increasing evidence suggesting that chronic alcohol intake, like other addictive drugs, induces neuroinflammation and oxidative stress, disrupting glutamate homeostasis in the main brain areas related to drug addiction. This review explores the potential application of mesenchymal stem cells (MSCs)-based therapy for the treatment of AUD. MSCs secrete a broad array of anti-inflammatory and antioxidant molecules, thus, the administration of MSCs, or their secretome, could reduce neuroinflammation and oxidative stress in the brain. These effects correlate with an increase in the expression of the main glutamate transporter, GLT1, which, through the normalization of the extracellular glutamate levels, could mediate the inhibitory effect of MSCs' secretome on chronic alcohol consumption, thus highlighting GLT1 as a central target to reduce chronic alcohol consumption.
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Affiliation(s)
- Javiera Gallardo
- Center for Regenerative Medicine, Faculty of Medicine, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - Pablo Berríos-Cárcamo
- Center for Regenerative Medicine, Faculty of Medicine, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile
| | - Fernando Ezquer
- Center for Regenerative Medicine, Faculty of Medicine, Clínica Alemana-Universidad del Desarrollo, Santiago, Chile; Research Center for the Development of Novel Therapeutics Alternatives for Alcohol Use Disorders, Santiago, Chile.
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4
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Cao C, Zhang L, Liu F, Shen J. Therapeutic Benefits of Mesenchymal Stem Cells in Acute Respiratory Distress Syndrome: Potential Mechanisms and Challenges. J Inflamm Res 2022; 15:5235-5246. [PMID: 36120184 PMCID: PMC9473549 DOI: 10.2147/jir.s372046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 08/31/2022] [Indexed: 11/23/2022] Open
Abstract
Acute respiratory distress syndrome (ARDS) presents as a form of acute respiratory failure resulting from non-cardiogenic pulmonary edema due to excessive alveolocapillary permeability, which may be pulmonary or systemic in origin. In the last 3 years, the coronavirus disease 2019 pandemic has resulted in an increase in ARDS cases and highlighted the challenges associated with this syndrome, as well as the unacceptably high mortality rates and lack of effective treatments. Currently, clinical treatment remains primarily supportive, including mechanical ventilation and drug-based therapy. Mesenchymal stem cell (MSC) therapies are emerging as a promising intervention in patients with ARDS and have promising therapeutic effects and safety. The therapeutic mechanisms include modifying the immune response and assisting with tissue repair. This review provides an overview of the general properties of MSCs and outlines their role in mitigating lung injury and promoting tissue repair in ARDS. Finally, we summarize the current challenges in the study of translational MSC research and identify avenues by which the discipline may progress in the coming years.
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Affiliation(s)
- Chao Cao
- Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai, People's Republic of China.,Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Shanghai, People's Republic of China.,Shanghai Medical College Fudan University, Shanghai, People's Republic of China
| | - Lin Zhang
- Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai, People's Republic of China.,Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Fuli Liu
- Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai, People's Republic of China.,Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Shanghai, People's Republic of China
| | - Jie Shen
- Research Center for Chemical Injury, Emergency and Critical Medicine of Fudan University, Shanghai, People's Republic of China.,Key Laboratory of Chemical Injury, Emergency and Critical Medicine of Shanghai Municipal Health Commission, Shanghai, People's Republic of China.,Center of Emergency and Critical Medicine in Jinshan Hospital of Fudan University, Shanghai, People's Republic of China.,Shanghai Medical College Fudan University, Shanghai, People's Republic of China
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5
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Autologous Stem Cells for the Treatment of Chondral Injury and Disease. OPER TECHN SPORT MED 2022. [DOI: 10.1016/j.otsm.2022.150963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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6
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Kim GU, Sung SE, Kang KK, Choi JH, Lee S, Sung M, Yang SY, Kim SK, Kim YI, Lim JH, Seo MS, Lee GW. Therapeutic Potential of Mesenchymal Stem Cells (MSCs) and MSC-Derived Extracellular Vesicles for the Treatment of Spinal Cord Injury. Int J Mol Sci 2021; 22:13672. [PMID: 34948463 PMCID: PMC8703906 DOI: 10.3390/ijms222413672] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Revised: 12/14/2021] [Accepted: 12/18/2021] [Indexed: 12/15/2022] Open
Abstract
Spinal cord injury (SCI) is a life-threatening condition that leads to permanent disability with partial or complete loss of motor, sensory, and autonomic functions. SCI is usually caused by initial mechanical insult, followed by a cascade of several neuroinflammation and structural changes. For ameliorating the neuroinflammatory cascades, MSC has been regarded as a therapeutic agent. The animal SCI research has demonstrated that MSC can be a valuable therapeutic agent with several growth factors and cytokines that may induce anti-inflammatory and regenerative effects. However, the therapeutic efficacy of MSCs in animal SCI models is inconsistent, and the optimal method of MSCs remains debatable. Moreover, there are several limitations to developing these therapeutic agents for humans. Therefore, identifying novel agents for regenerative medicine is necessary. Extracellular vesicles are a novel source for regenerative medicine; they possess nucleic acids, functional proteins, and bioactive lipids and perform various functions, including damaged tissue repair, immune response regulation, and reduction of inflammation. MSC-derived exosomes have advantages over MSCs, including small dimensions, low immunogenicity, and no need for additional procedures for culture expansion or delivery. Certain studies have demonstrated that MSC-derived extracellular vesicles (EVs), including exosomes, exhibit outstanding chondroprotective and anti-inflammatory effects. Therefore, we reviewed the principles and patho-mechanisms and summarized the research outcomes of MSCs and MSC-derived EVs for SCI, reported to date.
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Affiliation(s)
- Gang-Un Kim
- Department of Orthopedic Surgery, Hanil General Hospital, 308 Uicheon-ro, Dobong-gu, Seoul 01450, Korea;
| | - Soo-Eun Sung
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Kyung-Ku Kang
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Joo-Hee Choi
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Sijoon Lee
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Minkyoung Sung
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Seung Yun Yang
- Department of Biomaterials Science, Life and Industry Convergence Institute, Pusan National University, Miryang 50463, Korea;
| | - Seul-Ki Kim
- Efficacy Evaluation Team, Food Science R&D Center, KolmarBNH CO., LTD, 61Heolleungro 8-gil, Seocho-gu, Seoul 06800, Korea;
| | | | - Ju-Hyeon Lim
- New Drug Development Center, Osong Medical Innovation Foundation, Chungbuk 28160, Korea;
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea
| | - Min-Soo Seo
- Department of Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), Daegu 41061, Korea; (S.-E.S.); (K.-K.K.); (J.-H.C.); (S.L.); (M.S.)
| | - Gun Woo Lee
- Cellexobio, Co. Ltd., Daegu 42415, Korea;
- Department of Orthopedic Surgery, Yeungnam University College of Medicine, Yeungnam University Medical Center, 170 Hyonchung-ro, Namgu, Daegu 42415, Korea
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7
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Sykova E, Cizkova D, Kubinova S. Mesenchymal Stem Cells in Treatment of Spinal Cord Injury and Amyotrophic Lateral Sclerosis. Front Cell Dev Biol 2021; 9:695900. [PMID: 34295897 PMCID: PMC8290345 DOI: 10.3389/fcell.2021.695900] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Accepted: 05/31/2021] [Indexed: 01/01/2023] Open
Abstract
Preclinical and clinical studies with various stem cells, their secretomes, and extracellular vesicles (EVs) indicate their use as a promising strategy for the treatment of various diseases and tissue defects, including neurodegenerative diseases such as spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS). Autologous and allogenic mesenchymal stem cells (MSCs) are so far the best candidates for use in regenerative medicine. Here we review the effects of the implantation of MSCs (progenitors of mesodermal origin) in animal models of SCI and ALS and in clinical studies. MSCs possess multilineage differentiation potential and are easily expandable in vitro. These cells, obtained from bone marrow (BM), adipose tissue, Wharton jelly, or even other tissues, have immunomodulatory and paracrine potential, releasing a number of cytokines and factors which inhibit the proliferation of T cells, B cells, and natural killer cells and modify dendritic cell activity. They are hypoimmunogenic, migrate toward lesion sites, induce better regeneration, preserve perineuronal nets, and stimulate neural plasticity. There is a wide use of MSC systemic application or MSCs seeded on scaffolds and tissue bridges made from various synthetic and natural biomaterials, including human decellularized extracellular matrix (ECM) or nanofibers. The positive effects of MSC implantation have been recorded in animals with SCI lesions and ALS. Moreover, promising effects of autologous as well as allogenic MSCs for the treatment of SCI and ALS were demonstrated in recent clinical studies.
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Affiliation(s)
- Eva Sykova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Dasa Cizkova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.,Centre for Experimental and Clinical Regenerative Medicine, University of Veterinary Medicine and Pharmacy in Kosice, Kosice, Slovakia
| | - Sarka Kubinova
- Department of Optical and Biophysical Systems, Institute of Physics of the Czech Academy of Sciences, Prague, Czechia
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8
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Barachini S, Montali M, Panvini FM, Carnicelli V, Gatti GL, Piolanti N, Bonicoli E, Scaglione M, Buda G, Parchi PD. Mesangiogenic Progenitor Cells Are Tissue Specific and Cannot Be Isolated From Adipose Tissue or Umbilical Cord Blood. Front Cell Dev Biol 2021; 9:669381. [PMID: 34291045 PMCID: PMC8287027 DOI: 10.3389/fcell.2021.669381] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Accepted: 05/24/2021] [Indexed: 11/17/2022] Open
Abstract
Mesangiogenic progenitor cells (MPCs) have been isolated from human bone marrow (BM) mononuclear cells. They attracted particular attention for the ability to differentiate into exponentially growing mesenchymal stromal cells while retaining endothelial differentiative potential. MPC power to couple mesengenesis and angiogenesis highlights their tissue regenerative potential and clinical value, with particular reference to musculoskeletal tissues regeneration. BM and adipose tissue represent the most promising adult multipotent cell sources for bone and cartilage repair, although discussion is still open on their respective profitability. Culture determinants, as well as tissues of origin, appeared to strongly affect the regenerative potential of cell preparations, making reliable methods for cell isolation and growth a prerequisite to obtain cell-based medicinal products. Our group had established a definite consistent protocol for MPC culture, and here, we present data showing MPCs to be tissue specific.
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Affiliation(s)
- Serena Barachini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Marina Montali
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Francesca M Panvini
- Sant'Anna School of Advanced Studies, Institute of Life Sciences, Pisa, Italy
| | - Vittoria Carnicelli
- Department of Surgical, Medical and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy
| | - Gian Luca Gatti
- Plastic and Reconstructive Surgery Unit, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Nicola Piolanti
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Enrico Bonicoli
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Michelangelo Scaglione
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Gabriele Buda
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Paolo D Parchi
- Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
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9
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Zha K, Li X, Yang Z, Tian G, Sun Z, Sui X, Dai Y, Liu S, Guo Q. Heterogeneity of mesenchymal stem cells in cartilage regeneration: from characterization to application. NPJ Regen Med 2021; 6:14. [PMID: 33741999 PMCID: PMC7979687 DOI: 10.1038/s41536-021-00122-6] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 02/01/2021] [Indexed: 01/31/2023] Open
Abstract
Articular cartilage is susceptible to damage but hard to self-repair due to its avascular nature. Traditional treatment methods are not able to produce satisfactory effects. Mesenchymal stem cells (MSCs) have shown great promise in cartilage repair. However, the therapeutic effect of MSCs is often unstable partly due to their heterogeneity. Understanding the heterogeneity of MSCs and the potential of different types of MSCs for cartilage regeneration will facilitate the selection of superior MSCs for treating cartilage damage. This review provides an overview of the heterogeneity of MSCs at the donor, tissue source and cell immunophenotype levels, including their cytological properties, such as their ability for proliferation, chondrogenic differentiation and immunoregulation, as well as their current applications in cartilage regeneration. This information will improve the precision of MSC-based therapeutic strategies, thus maximizing the efficiency of articular cartilage repair.
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Affiliation(s)
- Kangkang Zha
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xu Li
- Musculoskeletal Research Laboratory, Department of Orthopedics and Traumatology, Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Zhen Yang
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Guangzhao Tian
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Zhiqiang Sun
- Medical School of Chinese PLA, Beijing, China
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xiang Sui
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
| | - Yongjing Dai
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China
| | - Shuyun Liu
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China.
| | - Quanyi Guo
- Institute of Orthopaedics, Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopaedics, Key Laboratory of Musculoskeletal Trauma & War Injuries, PLA, Beijing, China.
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10
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Wright A, Arthaud-Day ML, Weiss ML. Therapeutic Use of Mesenchymal Stromal Cells: The Need for Inclusive Characterization Guidelines to Accommodate All Tissue Sources and Species. Front Cell Dev Biol 2021; 9:632717. [PMID: 33665190 PMCID: PMC7921162 DOI: 10.3389/fcell.2021.632717] [Citation(s) in RCA: 94] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Accepted: 01/07/2021] [Indexed: 12/12/2022] Open
Abstract
Following their discovery over 50 years ago, mesenchymal stromal cells (MSCs) have become one of the most studied cellular therapeutic products by both academia and industry due to their regenerative potential and immunomodulatory properties. The promise of MSCs as a therapeutic modality has been demonstrated by preclinical data yet has not translated to consistent, successful clinical trial results in humans. Despite the disparities across the field, MSC shareholders are unified under one common goal-to use MSCs as a therapeutic modality to improve the quality of life for those suffering from a malady in which the standard of care is suboptimal or no longer effective. Currently, there is no Food and Drug Administration (FDA)-approved MSC therapy on the market in the United States although several MSC products have been granted regulatory approval in other countries. In this review, we intend to identify hurdles that are impeding therapeutic progress and discuss strategies that may aid in accomplishing this universal goal of widespread therapeutic use.
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Affiliation(s)
- Adrienne Wright
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, United States
| | - Marne L Arthaud-Day
- Department of Management, Kansas State University, Manhattan, KS, United States
| | - Mark L Weiss
- Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, United States.,Midwest Institute of Comparative Stem Cell Biotechnology, Kansas State University, Manhattan, KS, United States
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11
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Abstract
Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.
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Affiliation(s)
- Liyi Huang
- Department of Rehabilitation Medicine Center, 34753West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, PR China.,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, Sichuan Province, PR China
| | - Chenying Fu
- State Key Laboratory of Biotherapy, 34753West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Feng Xiong
- Department of Rehabilitation Medicine Center, 34753West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, PR China.,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, Sichuan Province, PR China
| | - Chengqi He
- Department of Rehabilitation Medicine Center, 34753West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, PR China.,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, Sichuan Province, PR China
| | - Quan Wei
- Department of Rehabilitation Medicine Center, 34753West China Hospital/West China School of Medicine, Sichuan University, Chengdu, Sichuan, PR China.,Key Laboratory of Rehabilitation Medicine in Sichuan Province, Sichuan University, Chengdu, Sichuan Province, PR China
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12
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Lu M, Guo J, Wu B, Zhou Y, Wu M, Farzaneh M, Khoshnam SE. Mesenchymal Stem Cell-Mediated Mitochondrial Transfer: a Therapeutic Approach for Ischemic Stroke. Transl Stroke Res 2020; 12:212-229. [PMID: 32975692 DOI: 10.1007/s12975-020-00853-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 09/14/2020] [Accepted: 09/16/2020] [Indexed: 12/17/2022]
Abstract
Stroke is the leading cause of death and adult disability worldwide. Mitochondrial dysfunction is one of the hallmarks of stroke-induced neuronal death, and maintaining mitochondrial function is essential in cell survival and neurological progress following ischemic stroke. Stem cell-mediated mitochondrial transfer represents an emerging therapeutic approach for ischemic stroke. Accumulating evidence suggests that mesenchymal stem cells (MSCs) can directly transfer healthy mitochondria to damaged cells, and rescue mitochondrial damage-provoked tissue degeneration. This review summarizes the research on MSCs-mediated mitochondrial transfer as a therapeutic strategy against ischemic stroke.
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Affiliation(s)
- Meng Lu
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.,Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, 050091, China.,Department of Formulaology, Basic Medicine College, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Jindong Guo
- Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, 050091, China.,Department of Formulaology, Basic Medicine College, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Bowen Wu
- Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, 050091, China.,Department of Biochemistry, Basic Medicine College, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Yuhui Zhou
- Academy of Traditional Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou, 450046, China.,Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, 050091, China.,Department of Formulaology, Basic Medicine College, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China
| | - Mishan Wu
- Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang, 050091, China. .,Department of Formulaology, Basic Medicine College, Hebei University of Chinese Medicine, Shijiazhuang, 050200, China.
| | - Maryam Farzaneh
- Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Seyed Esmaeil Khoshnam
- Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
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13
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Chen L, Li Y, Chen W, Han N, Li K, Guo R, Liu Z, Xiao Y. Enhanced recruitment and hematopoietic reconstitution of bone marrow-derived mesenchymal stem cells in bone marrow failure by the SDF-1/CXCR4. J Tissue Eng Regen Med 2020; 14:1250-1260. [PMID: 32633015 DOI: 10.1002/term.3096] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 06/08/2020] [Accepted: 06/22/2020] [Indexed: 12/13/2022]
Abstract
Aplastic anemia (AA) is a bone marrow failure disease. It is difficult to treat AA, and in addition, relapses are common because of its complex disease pathogenesis. Allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) infusion is an effective and safe treatment option for the AA patients. However, it found that BMSCs infusion in AA patients is less than 30% effective. Therefore, the key to improve the efficacy of BMSCs treatment in these patients is to enhance their homing efficiency to the target sites. Studies have shown that stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) axis plays an important role in promoting BMSCs homing. In this study, human BMSCs were transduced with lentivirus stably expressing CXCR4-BMSCs. Transduced BMSCs resemble normal BMSCs in many ways. Migration ability of CXCR4-BMSCs toward SDF-1 was increased because of the overexpression of CXCR4. In the mice with bone marrow failure, the migration and colonization ability of CXCR4-BMSCs to the bone marrow was significantly improved as seen by IVIS imaging and FACS. The SDF-1 level in the bone marrow failure mice was significantly higher than in the normal mice. Thus, from our study, it is clear that after CXCR4-BMSCs were infused into mice with bone marrow failure, SDF-1 interacted with CXCR4 receptor, leading cells to migrate and colonize to bone marrow. Because of the high SDF-1 expression in mouse bone marrow and CXCR4 receptor expression in cells, BMSCs homing was increased.
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Affiliation(s)
- Lixuan Chen
- Department of Hematology, Jiangmen Central Hospital, Jiangmen, China
| | - Yonghua Li
- Department of Hematology, General Hospital of Southern Theatre Command of PLA, Guangzhou, China.,The First School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Wancheng Chen
- Department of Hematology, Jiangmen Central Hospital, Jiangmen, China
| | - Na Han
- Department of Hematology, General Hospital of Southern Theatre Command of PLA, Guangzhou, China
| | - Keke Li
- Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Rui Guo
- Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Guangdong Provincial Engineering and Technological Research Center for Drug Carrier Development, Department of Biomedical Engineering, Jinan University, Guangzhou, China
| | - Zenghui Liu
- Department of Hematology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yang Xiao
- Department of Hematology, Jiangmen Central Hospital, Jiangmen, China.,Translational Medicine Center, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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14
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Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci 2020; 77:2771-2794. [PMID: 31965214 PMCID: PMC7223321 DOI: 10.1007/s00018-020-03454-6] [Citation(s) in RCA: 327] [Impact Index Per Article: 65.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 01/02/2020] [Accepted: 01/03/2020] [Indexed: 02/06/2023]
Abstract
Mesenchymal stem cells (MSCs) have been extensively investigated for the treatment of various diseases. The therapeutic potential of MSCs is attributed to complex cellular and molecular mechanisms of action including differentiation into multiple cell lineages and regulation of immune responses via immunomodulation. The plasticity of MSCs in immunomodulation allow these cells to exert different immune effects depending on different diseases. Understanding the biology of MSCs and their role in treatment is critical to determine their potential for various therapeutic applications and for the development of MSC-based regenerative medicine. This review summarizes the recent progress of particular mechanisms underlying the tissue regenerative properties and immunomodulatory effects of MSCs. We focused on discussing the functional roles of paracrine activities, direct cell-cell contact, mitochondrial transfer, and extracellular vesicles related to MSC-mediated effects on immune cell responses, cell survival, and regeneration. This will provide an overview of the current research on the rapid development of MSC-based therapies.
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Affiliation(s)
- Xing-Liang Fan
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, 510080, People's Republic of China
| | - Yuelin Zhang
- Department of Emergency, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Road II, Guangzhou, 510080, People's Republic of China
| | - Xin Li
- Department of Emergency, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Road II, Guangzhou, 510080, People's Republic of China
| | - Qing-Ling Fu
- Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, 510080, People's Republic of China.
- Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, Guangdong, People's Republic of China.
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15
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Saud B, Malla R, Shrestha K. A Review on the Effect of Plant Extract on Mesenchymal Stem Cell Proliferation and Differentiation. Stem Cells Int 2019; 2019:7513404. [PMID: 31428160 PMCID: PMC6681598 DOI: 10.1155/2019/7513404] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/29/2019] [Indexed: 02/07/2023] Open
Abstract
Stem cell has immense potential in regenerative cellular therapy. Mesenchymal stem cells (MSCs) can become a potential attractive candidate for therapy due to its remarkable ability of self-renewal and differentiation into three lineages, i.e., ectoderm, mesoderm, and endoderm. Stem cell holds tremendous promises in the field of tissue regeneration and transplantation for disease treatments. Globally, medicinal plants are being used for the treatment and prevention of a variety of diseases. Phytochemicals like naringin, icariin, genistein, and resveratrol obtained from plants have been extensively used in traditional medicine for centuries. Certain bioactive compounds from plants increase the rate of tissue regeneration, differentiation, and immunomodulation. Several studies show that bioactive compounds from plants have a specific role (bioactive mediator) in regulating the rate of cell division and differentiation through complex signal pathways like BMP2, Runx2, and Wnt. The use of plant bioactive phytochemicals may also become promising in treating diseases like osteoporosis, neurodegenerative disorders, and other tissue degenerative disorders. Thus, the present review article is aimed at highlighting the roles and consequences of plant extracts on MSCs proliferation and desired lineage differentiations.
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Affiliation(s)
- Bhuvan Saud
- Central Department of Biotechnology, Tribhuvan University, Kirtipur, Nepal
- Faculty of Science, Nepal Academy of Science and Technology (NAST), Khumaltar, Lalitpur, Nepal
| | - Rajani Malla
- Central Department of Biotechnology, Tribhuvan University, Kirtipur, Nepal
| | - Kanti Shrestha
- Faculty of Science, Nepal Academy of Science and Technology (NAST), Khumaltar, Lalitpur, Nepal
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16
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Cizkova D, Murgoci AN, Cubinkova V, Humenik F, Mojzisova Z, Maloveska M, Cizek M, Fournier I, Salzet M. Spinal Cord Injury: Animal Models, Imaging Tools and the Treatment Strategies. Neurochem Res 2019; 45:134-143. [PMID: 31006093 DOI: 10.1007/s11064-019-02800-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 04/10/2019] [Accepted: 04/11/2019] [Indexed: 02/06/2023]
Abstract
Spinal cord injury (SCI) often leads to irreversible neuro-degenerative changes with life-long consequences. While there is still no effective therapy available, the results of past research have led to improved quality of life for patients suffering from partial or permanent paralysis. In this review we focus on the need, importance and the scientific value of experimental animal models simulating SCI in humans. Furthermore, we highlight modern imaging tools determining the location and extent of spinal cord damage and their contribution to early diagnosis and selection of appropriate treatment. Finally, we focus on available cellular and acellular therapies and novel combinatory approaches with exosomes and active biomaterials. Here we discuss the efficacy and limitations of adult mesenchymal stem cells which can be derived from bone marrow, adipose tissue or umbilical cord blood and its Wharton's jelly. Special attention is paid to stem cell-derived exosomes and smart biomaterials due to their special properties as a delivery system for proteins, bioactive molecules or even genetic material.
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Affiliation(s)
- Dasa Cizkova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 10, Bratislava, Slovakia. .,Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Kosice, Slovakia. .,Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Université de Lille, 59000, Lille, France.
| | - Adriana-Natalia Murgoci
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 10, Bratislava, Slovakia.,Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Université de Lille, 59000, Lille, France
| | - Veronika Cubinkova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Dúbravská cesta 9, 845 10, Bratislava, Slovakia
| | - Filip Humenik
- Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Kosice, Slovakia
| | - Zuzana Mojzisova
- Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Kosice, Slovakia
| | - Marcela Maloveska
- Department of Anatomy, Histology and Physiology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Kosice, Slovakia
| | - Milan Cizek
- Department of Epizootology and Parasitology, University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Kosice, Slovakia
| | - Isabelle Fournier
- Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Université de Lille, 59000, Lille, France
| | - Michel Salzet
- Inserm, U-1192-Laboratoire Protéomique, Réponse Inflammatoire et Spectrométrie de Masse-PRISM, Université de Lille, 59000, Lille, France
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17
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Stem Cells for Osteochondral Regeneration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1059:219-240. [DOI: 10.1007/978-3-319-76735-2_10] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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18
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Zhang H, Li ZL, Su XZ, Ding L, Li J, Zhu H. Subchondral bone derived mesenchymal stem cells display enhanced osteo-chondrogenic differentiation, self-renewal and proliferation potentials. Exp Anim 2018. [PMID: 29515059 PMCID: PMC6083032 DOI: 10.1538/expanim.17-0137] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Rabbit mesenchymal stem cells (MSCs) are important seed cells in regenerative medicine research, particularly in translational research. In the current study, we showed that rabbit subchondral bone is a reliable source of MSCs. First, we harvested subchondral bone (SCB) from the rabbit knee-joint and initiated the MSC culture by cultivating enzyme-treated SCB. Adherent fibroblast-like cells that outgrew from SCB fulfill the common immuno-phenotypic criteria for defining MSCs, but with low contamination of CD45+ hematopoietic cells. Interestingly, differentiated SCB-MSCs expressed osteogenic and chondrogenic markers at significantly higher levels than those in bone marrow cell suspension-derived MSCs (BMS-MSCs) (P<0.05). No differences in the expression of adipogenic markers between SCB-MSC and BMS-MSC (P>0.05) were observed. Moreover, the results of the colony forming unit-fibroblast assay and sphere formation assay demonstrated that the SCB-MSCs had increased self-renewal potential. SCB-MSCs expressed higher levels of the stemness markers Nanog, OCT4, and Sox-2 compared to in BMS-MSCs (P<0.05). Furthermore, the results of both the CCK-8-based assay and CFSE dilution assay showed that SCB-MSCs exhibited enhanced proliferative capacity. In addition, SCB-MSCs exhibited higher phosphorylation of extracellular signal-related kinase/mitogen-activated protein kinase signaling, which is closely related to MSC proliferation. In conclusion, we identified SCB-MSCs as a novel stem cell population that met the requirements of MSCs; the unique properties of SCB-MSC are important for the potential treatment of tissue damage resulting from disease and trauma.
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Affiliation(s)
- Hao Zhang
- Department of Orthopedics, Sports Medicine Center, People's Liberation Army General Hospital, No. 28 Fu Xing Road, Haidian District, Beijing 100853, P.R. China.,Department of Cell Biology, Institute of Basic Medical Sciences, No. 27 Tai Ping Road, Haidian District, Beijing 100850, P.R. China
| | - Zhong-Li Li
- Department of Orthopedics, Sports Medicine Center, People's Liberation Army General Hospital, No. 28 Fu Xing Road, Haidian District, Beijing 100853, P.R. China
| | - Xiang-Zheng Su
- Department of Orthopedics, Sports Medicine Center, People's Liberation Army General Hospital, No. 28 Fu Xing Road, Haidian District, Beijing 100853, P.R. China
| | - Li Ding
- Department of Hematology, General Hospital of Air Forces, PLA, No. 30 Fu Cheng Road, Haidian District, Beijing 100142, P.R. China
| | - Ji Li
- Department of Orthopedics, Sports Medicine Center, People's Liberation Army General Hospital, No. 28 Fu Xing Road, Haidian District, Beijing 100853, P.R. China
| | - Heng Zhu
- Department of Cell Biology, Institute of Basic Medical Sciences, No. 27 Tai Ping Road, Haidian District, Beijing 100850, P.R. China
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19
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Anz AW, Pinegar CO. The Role of Stem Cells in Surgical Repair. CARTILAGE RESTORATION 2018:151-164. [DOI: 10.1007/978-3-319-77152-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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20
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Xu L, Liu Y, Sun Y, Wang B, Xiong Y, Lin W, Wei Q, Wang H, He W, Wang B, Li G. Tissue source determines the differentiation potentials of mesenchymal stem cells: a comparative study of human mesenchymal stem cells from bone marrow and adipose tissue. Stem Cell Res Ther 2017; 8:275. [PMID: 29208029 PMCID: PMC5718061 DOI: 10.1186/s13287-017-0716-x] [Citation(s) in RCA: 201] [Impact Index Per Article: 25.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Revised: 08/09/2017] [Accepted: 10/30/2017] [Indexed: 12/20/2022] Open
Abstract
Background Mesenchymal stem cells (MSCs) possess intrinsic regeneration capacity as part of the repair process in response to injury, such as fracture or other tissue injury. Bone marrow and adipose tissue are the major sources of MSCs. However, which cell type is more effective and suitable for cell therapy remains to be answered. The intrinsic molecular mechanism supporting the assertion has also been lacking. Methods Human bone marrow-derived MSCs (BMSCs) and adipose tissue-derived MSCs (ATSCs) were isolated from bone marrow and adipose tissue obtained after total hip arthroplasty. ATSCs and BMSCs were incubated in standard growth medium. Trilineage differentiation including osteogenesis, adipogenesis, and chondrogenesis was performed by addition of relevant induction mediums. The expression levels of trilineage differentiation marker genes were evaluated by quantitative RT-PCR. The methylation status of CpG sites of Runx2, PPARγ, and Sox9 promoters were checked by bisulfite sequencing. In addition, ectopic bone formation and calvarial bone critical defect models were used to evaluate the bone regeneration ability of ATSCs and BMSCs in vivo. Results The results showed that BMSCs possessed stronger osteogenic and lower adipogenic differentiation potentials compared to ATSCs. There was no significant difference in the chondrogenic differentiation potential. The CpG sites of Runx2 promoter in BMSCs were hypomethylated, while in ATSCs they were hypermethylated. The CpG sites of PPARγ promoter in ATSCs were hypomethylated, while in BMSCs they were hypermethylated. The methylation status of Sox9 promoter in BMSCs was only slightly lower than that in ATSCs. Conclusions The epigenetic memory obtained from either bone marrow or adipose tissue favored MSC differentiation along an osteoblastic or adipocytic lineage. The methylation status of the main transcription factors controlling MSC fate contributes to the differential differentiation capacities of different source-derived MSCs. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0716-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Liangliang Xu
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China.,Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China
| | - Yamei Liu
- Departments of Diagnostics of Traditional Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, 510006, People's Republic of China
| | - Yuxin Sun
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China
| | - Bin Wang
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China
| | - Yunpu Xiong
- Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, 510240, People's Republic of China
| | - Weiping Lin
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China
| | - Qiushi Wei
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haibin Wang
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei He
- Key Laboratory of Orthopaedics & Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China. .,Department of Traumatology, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
| | - Bin Wang
- Department of Traumatology, The Third Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, Guangdong, 510240, People's Republic of China.
| | - Gang Li
- Department of Orthopaedics & Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China. .,Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. .,Stem Cells and Regenerative Medicine Laboratory, Lui Che Woo Institute of Innovative Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, Special Administrative Region of China. .,The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People's Republic of China. .,Room 904, 9/F, Li Ka Shing Institute of Health Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, Special Administrative Region of China.
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21
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Advances of Stem Cell Therapeutics in Cutaneous Wound Healing and Regeneration. Mediators Inflamm 2017; 2017:5217967. [PMID: 29213192 PMCID: PMC5682068 DOI: 10.1155/2017/5217967] [Citation(s) in RCA: 142] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2017] [Revised: 08/14/2017] [Accepted: 09/13/2017] [Indexed: 12/15/2022] Open
Abstract
Cutaneous wound healing is a complex multiple phase process, which overlaps each other, where several growth factors, cytokines, chemokines, and various cells interact in a well-orchestrated manner. However, an imbalance in any of these phases and factors may lead to disruption in harmony of normal wound healing process, resulting in transformation towards chronic nonhealing wounds and abnormal scar formation. Although various therapeutic interventions are available to treat chronic wounds, current wound-care has met with limited success. Progenitor stem cells possess potential therapeutic ability to overcome limitations of the present treatments as it offers accelerated wound repair with tissue regeneration. A substantial number of stem cell therapies for cutaneous wounds are currently under development as a result of encouraging preliminary findings in both preclinical and clinical studies. However, the mechanisms by which these stem cells contribute to the healing process have yet to be elucidated. In this review, we emphasize on the major treatment modalities currently available for the treatment of the wound, role of various interstitial stem cells and exogenous adult stem cells in cutaneous wound healing, and possible mechanisms involved in the healing process.
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22
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Mushahary D, Spittler A, Kasper C, Weber V, Charwat V. Isolation, cultivation, and characterization of human mesenchymal stem cells. Cytometry A 2017; 93:19-31. [PMID: 29072818 DOI: 10.1002/cyto.a.23242] [Citation(s) in RCA: 383] [Impact Index Per Article: 47.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 08/28/2017] [Indexed: 12/14/2022]
Abstract
Mesenchymal stem cells (MSC) exhibit a high self-renewal capacity, multilineage differentiation potential and immunomodulatory properties. This set of exceptional features makes them an attractive tool for research and clinical application. However, MSC are far from being a uniform cell type, which makes standardization difficult. The exact properties of human MSC (hMSC) can vary greatly depending on multiple parameters including tissue source, isolation method and medium composition. In this review we address the most important influence factors. We highlight variations in the differentiation potential of MSC from different tissue sources. Furthermore, we compare enzymatic isolation strategies with explants cultures focusing on adipose tissue and umbilical cords as two relevant examples. Additionally, we address effects of medium composition and serum supplementation on MSC expansion and differentiation. The lack of standardized methods for hMSC isolation and cultivation mandates careful evaluation of different protocols regarding efficiency and cell quality. MSC characterization based on a set of minimal criteria defined by the International Society for Cellular Therapy is a widely accepted practice, and additional testing for MSC functionality can provide valuable supplementary information. The MSC secretome has been identified as an important signaling mechanism to affect other cells. In this context, extracellular vesicles (EVs) are attracting increasing interest. The thorough characterization of MSC-derived EVs and their interaction with target cells is a crucial step toward a more complete understanding of MSC-derived EV functionality. Here, we focus on flow cytometric approaches to characterize free as well as cell bound EVs and address potential differences in the bioactivity of EVs derived from stem cells from different sources. © 2017 International Society for Advancement of Cytometry.
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Affiliation(s)
- Dolly Mushahary
- Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria
| | - Andreas Spittler
- Core Facility Flow Cytometry & Surgical Research Laboratories, Medical University of Vienna, 1090 Vienna, Austria
| | - Cornelia Kasper
- Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria
| | - Viktoria Weber
- Christian Doppler Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, 3500 Krems, Austria
| | - Verena Charwat
- Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria
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23
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Mahmoud EE, Tanaka Y, Kamei N, Harada Y, Ohdan H, Adachi N, Ochi M. Monitoring immune response after allogeneic transplantation of mesenchymal stem cells for osteochondral repair. J Tissue Eng Regen Med 2017; 12:e275-e286. [DOI: 10.1002/term.2413] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Revised: 12/12/2016] [Accepted: 01/13/2017] [Indexed: 12/19/2022]
Affiliation(s)
- Elhussein Elbadry Mahmoud
- Department of Orthopaedic Surgery, Integrated Health Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
- Department of Surgery, Faculty of Veterinary Medicine; South Valley University; Qena Egypt
| | - Yuka Tanaka
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
| | - Naosuke Kamei
- Department of Orthopaedic Surgery, Integrated Health Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
- Medical Center for Translational and Clinical Research; Hiroshima University Hospital; Hiroshima Japan
| | - Yohei Harada
- Department of Orthopaedic Surgery, Integrated Health Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
| | - Nobuo Adachi
- Department of Orthopaedic Surgery, Integrated Health Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
| | - Mitsuo Ochi
- Department of Orthopaedic Surgery, Integrated Health Sciences; Institute of Biomedical & Health Sciences, Hiroshima University; Hiroshima Japan
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24
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Xie M, Qin H, Luo Q, He X, He X, Lan P, Lian L. Comparison of Adipose-Derived and Bone Marrow Mesenchymal Stromal Cells in a Murine Model of Crohn's Disease. Dig Dis Sci 2017; 62:115-123. [PMID: 27107864 DOI: 10.1007/s10620-016-4166-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 04/03/2016] [Indexed: 12/18/2022]
Abstract
BACKGROUND Mesenchymal stromal cells (MSCs) have been used in the treatment of Crohn's disease (CD) because of the immunomodulatory ability. AIM The aim of this study was to investigate the therapeutic effect of adipose-derived MSCs (AD-MSCs) and to compare the therapeutic effect of AD-MSCs with that of bone marrow MSCs (BM-MSCs) in a murine model of CD. METHODS Murine colitis model of CD was created by trinitrobenzene sulfonic acid (TNBS). Twelve hours after treatment with TNBS, the mouse model was injected with MSCs intraperitoneally. Real-time polymerase chain reaction and immunohistochemistry staining were used to measure the expression levels of inflammatory cytokines in colonic tissues to investigate the therapeutic effect of AD-MSCs. The ten-day survival was recorded after infusion of MSCs. RESULTS Intraperitoneal injection of MSCs alleviated the clinical and histopathologic severity of intestinal inflammation, and improved the survival of the TNBS-induced mouse model of CD. AD-MSCs could effectively increase the expression of interleukin-10 and reduce the secretion of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-12, and vascular endothelial growth factor. The mucosal injury was repaired by AD-MSCs. These effects were comparable between AD-MSCs and BM-MSCs. CONCLUSIONS The therapeutic effect appears similar between AD-MSCs and BM-MSCs in treating CD. AD-MSCs may be a potential alternative of cell-based therapy for CD.
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Affiliation(s)
- Minghao Xie
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Huabo Qin
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Qianxin Luo
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Xiaosheng He
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Xiaowen He
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Ping Lan
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China.,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China
| | - Lei Lian
- Department of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, 26 Yuancun Erheng Rd, Guangzhou, 510655, Guangdong, People's Republic of China. .,Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.
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El-Badawy A, Amer M, Abdelbaset R, Sherif SN, Abo-Elela M, Ghallab YH, Abdelhamid H, Ismail Y, El-Badri N. Adipose Stem Cells Display Higher Regenerative Capacities and More Adaptable Electro-Kinetic Properties Compared to Bone Marrow-Derived Mesenchymal Stromal Cells. Sci Rep 2016; 6:37801. [PMID: 27883074 PMCID: PMC5121630 DOI: 10.1038/srep37801] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2016] [Accepted: 11/02/2016] [Indexed: 12/12/2022] Open
Abstract
Adipose stem cells (ASCs) have recently emerged as a more viable source for clinical applications, compared to bone-marrow mesenchymal stromal cells (BM-MSCs) because of their abundance and easy access. In this study we evaluated the regenerative potency of ASCs compared to BM-MSCs. Furthermore, we compared the dielectric and electro-kinetic properties of both types of cells using a novel Dielectrophoresis (DEP) microfluidic platform based on a printed circuit board (PCB) technology. Our data show that ASCs were more effective than BM-MSCs in promoting neovascularization in an animal model of hind-limb ischemia. When compared to BM-MSCs, ASCs displayed higher resistance to hypoxia-induced apoptosis, and to oxidative stress-induced senescence, and showed more potent proangiogenic activity. mRNA expression analysis showed that ASCs had a higher expression of Oct4 and VEGF than BM-MSCs. Furthermore, ASCs showed a remarkably higher telomerase activity. Analysis of the electro-kinetic properties showed that ASCs displayed different traveling wave velocity and rotational speed compared to BM-MSCs. Interestingly, ASCs seem to develop an adaptive response when exposed to repeated electric field stimulation. These data provide new insights into the physiology of ASCs, and evidence to their potential superior potency compared to marrow MSCs as a source of stem cells.
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Affiliation(s)
- Ahmed El-Badawy
- Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, Egypt
| | - Marwa Amer
- Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, Egypt
| | - Reda Abdelbaset
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt.,Department of Biomedical Engineering, Helwan University, Cairo, Egypt
| | - Sameh N Sherif
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt.,Department of Biomedical Engineering, Helwan University, Cairo, Egypt
| | - Marwan Abo-Elela
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt
| | - Yehya H Ghallab
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt.,Department of Biomedical Engineering, Helwan University, Cairo, Egypt
| | - Hamdy Abdelhamid
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt
| | - Yehea Ismail
- Center of Nanoelectronics and Devices (CND), Zewail City of Science and Technology/American University in Cairo, Cairo, Egypt
| | - Nagwa El-Badri
- Center of Excellence for Stem Cells and Regenerative Medicine (CESC), Zewail City of Science and Technology, Egypt
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26
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Li CY, Wu XY, Tong JB, Yang XX, Zhao JL, Zheng QF, Zhao GB, Ma ZJ. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther 2015; 6:55. [PMID: 25884704 PMCID: PMC4453294 DOI: 10.1186/s13287-015-0066-5] [Citation(s) in RCA: 293] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 11/24/2014] [Accepted: 03/25/2015] [Indexed: 12/15/2022] Open
Abstract
INTRODUCTION Mesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications. METHODS The bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects). RESULTS Under human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem cell-derived factor-1). Adipose tissue-derived MSCs had more potent immunomodulatory effects than bone marrow-derived MSCs. CONCLUSIONS Adipose tissue-derived MSCs have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects, but bone marrow-derived MSCs have advantages in osteogenic and chondrogenic differentiation potential and secreted proteins (stem cell-derived factor-1 and hepatocyte growth factor); these biological advantages should be considered systematically when choosing the MSC source for specific clinical application.
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Affiliation(s)
- Chun-yu Li
- China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China. .,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China.
| | - Xiao-yun Wu
- Beijing Institute of Life Science Translational Medicine Research Center, Beijing, 100085, China.
| | - Jia-bei Tong
- Shandong Medicinal Biotechnology Centre, Shandong Academy of Medical Sciences, Jinan, 250000, China.
| | - Xin-xin Yang
- School of Pharmacy, Changchun University of Traditional Chinese Medicine, Changsha, 410208, China.
| | - Jing-li Zhao
- Jilin Vocational College of Industry and Technology, Jilin, 132013, China.
| | - Quan-fu Zheng
- China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, 100039, China. .,School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 610000, China.
| | - Guo-bin Zhao
- The First Affiliated Hospital, Hebei North University, Zhangjiakou, 075000, China.
| | - Zhi-jie Ma
- Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity. Expert Rev Mol Med 2014; 16:e9. [PMID: 24810570 PMCID: PMC4017835 DOI: 10.1017/erm.2014.9] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The identification of multipotent adipose-derived stromal cells (ASC) has raised hope that tissue regeneration approaches established with bone-marrow-derived stromal cells (BMSC) can be reproduced with a cell-type that is far more accessible in large quantities. Recent detailed comparisons, however, revealed subtle functional differences between ASC and BMSC, stressing the concept of a common mesenchymal progenitor existing in a perivascular niche across all tissues. Focussing on bone and cartilage repair, this review summarises recent in vitro and in vivo studies aiming towards tissue regeneration with ASC. Advantages of good accessibility, high yield and superior growth properties are counterbalanced by an inferiority of ASC to form ectopic bone and stimulate long-bone healing along with their less pronounced osteogenic and angiogenic gene expression signature. Hence, particular emphasis is placed on establishing whether stem cell activity of ASC is so far proven and relevant for successful osteochondral regeneration, or whether trophic activity may largely determine therapeutic outcome.
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28
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Rasi Ghaemi S, Harding FJ, Delalat B, Gronthos S, Voelcker NH. Exploring the mesenchymal stem cell niche using high throughput screening. Biomaterials 2013; 34:7601-15. [DOI: 10.1016/j.biomaterials.2013.06.022] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2013] [Accepted: 06/12/2013] [Indexed: 12/13/2022]
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29
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McIntosh KR, Frazier T, Rowan BG, Gimble JM. Evolution and future prospects of adipose-derived immunomodulatory cell therapeutics. Expert Rev Clin Immunol 2013; 9:175-84. [PMID: 23390948 DOI: 10.1586/eci.12.96] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Over the past two decades, tissue engineering and regenerative medicine have evolved from what many considered a theoretical science to what is now a clinical reality. Tissue engineering combines biomaterial scaffolds, growth factors and stem or progenitor cells to repair damaged tissues. Adipose tissue, an abundant and easily accessed tissue, is a potential source of stromal/stem cells for regenerative therapeutic applications. Like bone marrow-derived mesenchymal stem cells, adipose-derived stromal/stem cells display both immunomodulatory and immunosuppressive properties. The adipose cells exert these actions, in part, through their secretion of paracrine growth factors. This review highlights recent developments in the isolation, characterization and preclinical application of adipose-derived cells and the challenges facing their translation into clinical practice.
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30
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Increase of chondrogenic potentials in adipose-derived stromal cells by co-delivery of type I and type II TGFβ receptors encoding bicistronic vector system. J Control Release 2012; 160:577-82. [PMID: 22522074 DOI: 10.1016/j.jconrel.2012.04.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Revised: 04/04/2012] [Accepted: 04/05/2012] [Indexed: 11/22/2022]
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31
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Erdman CP, Dosier CR, Olivares-Navarrete R, Baile C, Guldberg RE, Schwartz Z, Boyan BD. Effects of resveratrol on enrichment of adipose-derived stem cells and their differentiation to osteoblasts in two-and three-dimensional cultures. J Tissue Eng Regen Med 2012; 6 Suppl 3:s34-46. [PMID: 22467433 DOI: 10.1002/term.513] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Revised: 04/06/2011] [Accepted: 08/27/2011] [Indexed: 01/05/2023]
Abstract
The goal of this study was to develop a method for increasing the yield of multipotent adipose-derived mesenchymal stem cells (ASCs) and osteoprogenitor cells (OPCs) from subcutaneous fat. After removing mature adipocytes and haematopoietic cells from rat inguinal fat, ASCs in the remaining cell population were verified by their attachment to plastic, surface marker profile (CD271(+), CD73(+) and CD45(-)) and ability to differentiate into adipocytes, chondrocytes and osteoblasts. OPCs were defined as E11(+) and OCN(+). Adherent cells were cultured in growth medium (GM) or osteogenic medium (OM) and treated with resveratrol (0, 12.5, and 25 µM) for 7 days; ASCs and OPCs were assessed by flow cytometry. Osteogenic potential was determined in two-dimensional (2D) cultures as a function of alkaline phosphatase-specific activity and osteocalcin production. In addition, cells were seeded onto three-dimensional (3D) poly-ε-caprolactone scaffolds and cultured under dynamic conditions; mineralization was quantified by micro-CT at 4, 8 and 12 weeks. Resveratrol increased the percentage of ASCs in the population (population%) and number of ASCs in both GM and OM, but increased only the number of OPCs in GM. In both media types resveratrol increased alkaline phosphatase activity and osteocalcin levels. In 3D cultures, resveratrol-treated cells significantly increased mineralized matrix volume at early time points. Resveratrol exerted a biphasic effect on adherent cells by enriching the ASC and OPC populations and enhancing osteogenic differentiation. Resveratrol pretreatment induced more mineralization at earlier time points and represents a clinically viable technique for orthopaedic and dental applications for autologous stem cell therapy.
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Affiliation(s)
- Christopher P Erdman
- Parker H Petit Institute for Bioengineering and Bioscience, Georgia, Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA
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Mesenchymal stem cells: characteristics, sources, and mechanisms of action. Vet Clin North Am Equine Pract 2012; 27:243-61. [PMID: 21872757 DOI: 10.1016/j.cveq.2011.06.004] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
This article provides an overview of mesenchymal stem cell (MSC) biology. In the first section, the characteristics that are routinely used to define MSCs-adherence, proliferation, multi-lineage potential, and "cluster of differentiation" marker profiles-are discussed. In the second section, the major tissues and body fluids that are used as sources for equine MSCs are presented, along with the comparative biologic activities of MSCs from specific locations. Finally, the current understanding of the mechanisms by which MSCs influence repair and regeneration are discussed, with an emphasis on the clinical importance of MSC trophic activities.
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33
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34
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Hildner F, Albrecht C, Gabriel C, Redl H, van Griensven M. State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med 2011; 5:e36-51. [PMID: 21413156 DOI: 10.1002/term.386] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2010] [Accepted: 10/21/2010] [Indexed: 12/15/2022]
Abstract
Trauma, malposition and age-related degeneration of articular cartilage often result in severe lesions that do not heal spontaneously. Many efforts over the last centuries have been undertaken to support cartilage healing, with approaches ranging from symptomatic treatment to structural cartilage regeneration. Microfracture and matrix-associated autologous chondrocyte transplantation (MACT) can be regarded as one of the most effective techniques available today to treat traumatic cartilage defects. Research is focused on the development of new biomaterials, which are intended to provide optimized physical and biochemical conditions for cell proliferation and cartilage synthesis. New attempts have also been undertaken to replace chondrocytes with cells that are more easily available and cause less donor site morbidity, e.g. adipose derived stem cells (ASC). The number of in vitro studies on adult stem cells has rapidly increased during the last decade, indicating that many variables have yet to be optimized to direct stem cells towards the desired lineage. The present review gives an overview of the difficulties of cartilage repair and current cartilage repair techniques. Moreover, it reviews new fields of cartilage tissue engineering, including stem cells, co-cultures and platelet-rich plasma (PRP).
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Affiliation(s)
- F Hildner
- Red Cross Blood Transfusion Service of Upper Austria, Linz, Austria.
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35
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Vinardell T, Buckley CT, Thorpe SD, Kelly DJ. Composition-function relations of cartilaginous tissues engineered from chondrocytes and mesenchymal stem cells isolated from bone marrow and infrapatellar fat pad. J Tissue Eng Regen Med 2010; 5:673-83. [DOI: 10.1002/term.357] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2010] [Accepted: 07/12/2010] [Indexed: 12/18/2022]
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