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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17:98693. [DOI: 10.4252/wjsc.v17.i2.98693] [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: 07/04/2024] [Revised: 12/09/2024] [Accepted: 01/23/2025] [Indexed: 02/24/2025] Open
Abstract
Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle, leading to a reduction or loss of muscle fibers. This condition not only significantly impacts patients’ quality of life but also imposes substantial socioeconomic burdens. The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options. Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition. This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies, focusing on mesenchymal stem cells, induced pluripotent stem cells, and their derivatives. Additionally, the challenges these stem cells face in clinical applications are discussed. A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.
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Affiliation(s)
- Ying-Jie Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Ze-Hao Chen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Yun-Tian Shen
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Ke-Xin Wang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Yi-Min Han
- Medical College, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Chen Zhang
- Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Nantong University, Nantong 226000, Jiangsu Province, China
| | - Xiao-Ming Yang
- Co-Innovation Center of Neuroregeneration, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Nantong University, Nantong 226000, Jiangsu Province, China
- Research and Development Center for E-Learning, Ministry of Education, Beijing 100816, China
| | - Bing-Qian Chen
- Department of Orthopaedics, Changshu Hospital Affiliated to Soochow University, Changshu 215500, Jiangsu Province, China
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Jeong DH, Kim MJ, Park CH. Effect of Combining Exercise with Adipose-Derived Mesenchymal Stem Cells in Muscle Atrophy Model of Sarcopenia. Int J Mol Sci 2025; 26:451. [PMID: 39859165 PMCID: PMC11764817 DOI: 10.3390/ijms26020451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2024] [Revised: 12/28/2024] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
Deterioration in muscle mass, strength, and physical performance due to conditions such as sarcopenia can affect daily activities and quality of life in the elderly. Exercise and mesenchymal stem cells (MSCs) are potential therapies for sarcopenia. This study evaluates the combined effects of exercise and adipose-derived MSCs (ADMSCs) in aged rats with sarcopenia. Eighteen-month-old rats were randomly divided into four groups: control, exercise (Ex), ADMSCs injection (MSC), and ADMSCs injection with exercise (MSC + Ex). Gastrocnemius (GCM) muscle mass increased in the Ex, MSC, and MSC + Ex groups compared to the control group. Although the mean CSA did not differ significantly between the groups, the size distribution of myofibers shifted toward larger sizes in the Ex and MSC + Ex groups. The MSC + Ex group performed best in functional tests, including the rotarod and hot plate tests. The protein expression levels of tumor necrosis factor (TNF) and the p-AMP-activated protein kinase (AMPK)/AMPK ratio in the GCM muscle were the lowest in the MSC + Ex group. This study demonstrates that combining exercise and ADMSC interventions was the most effective treatment for aged sarcopenic rats, suggesting a potential synergistic approach for sarcopenia treatment.
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Affiliation(s)
- Dong-Hwa Jeong
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea;
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
| | - Min-Jeong Kim
- Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea
- Research Institute for Future Medicine, Samsung Medical Center, Seoul 06351, Republic of Korea
| | - Chul-Hyun Park
- Department of Physical and Rehabilitation Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea;
- Medical Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, Republic of Korea
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Sanz-Nogués C, Keane AJ, Creane M, Hynes SO, Chen X, Lyons CJ, Horan E, Elliman SJ, Goljanek-Whysall K, O’Brien T. Mesenchymal stromal cell transplantation ameliorates fibrosis and microRNA dysregulation in skeletal muscle ischemia. Stem Cells 2024; 42:976-991. [PMID: 39283740 PMCID: PMC11541228 DOI: 10.1093/stmcls/sxae058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 08/23/2024] [Indexed: 11/08/2024]
Abstract
Peripheral arterial disease (PAD) is associated with lower-extremity muscle wasting. Hallmark features of PAD-associated skeletal muscle pathology include loss of skeletal muscle mass, reduced strength and physical performance, increased inflammation, fibrosis, and adipocyte infiltration. At the molecular level, skeletal muscle ischemia has also been associated with gene and microRNA (miRNA) dysregulation. Mesenchymal stromal cells (MSCs) have been shown to enhance muscle regeneration and improve muscle function in various skeletal muscle injuries. This study aimed to evaluate the effects of intramuscularly delivered human umbilical cord-derived MSCs (hUC-MSCs) on skeletal muscle ischemia. Herein, we report an hUC-MSC-mediated amelioration of ischemia-induced skeletal muscle atrophy and function via enhancement of myofiber regeneration, reduction of tissue inflammation, adipocyte accumulation, and tissue fibrosis. These changes were observed in the absence of cell-mediated enhancement of blood flow recovery as measured by laser Doppler imaging. Furthermore, reduced tissue fibrosis in the hUC-MSC-treated group was associated with upregulation of miR-1, miR-133a, and miR-29b and downregulation of targeted pro-fibrotic genes such as Col1a1 and Fn1. Our results support the use of hUC-MSCs as a novel approach to reduce fibrosis and promote skeletal muscle regeneration after ischemic injury in patients with PAD.
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Affiliation(s)
- Clara Sanz-Nogués
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
- CÚRAM SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
| | - Alan J Keane
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
| | - Michael Creane
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
| | - Sean O Hynes
- Discipline of Pathology, University of Galway, Galway, Ireland
- Division of Anatomic Pathology, University Hospital Galway, Galway, Ireland
| | - Xizhe Chen
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
| | - Caomhán J Lyons
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
| | - Emma Horan
- Orbsen Therapeutics Ltd., Galway, Ireland
| | | | - Katarzyna Goljanek-Whysall
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
- Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, United Kingdom
| | - Timothy O’Brien
- Regenerative Medicine Institute (REMEDI), University of Galway, Galway, Ireland
- CÚRAM SFI Research Centre for Medical Devices, University of Galway, Galway, Ireland
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Deng J, Joshua Cohen D, Matias EB, Olson LC, McClure MJ, Boyan BD, Schwartz Z. Reduced osseointegration in disuse and denervation rat models results from impaired cellular responses to multiscale microstructured titanium surfaces. J Orthop Res 2024; 42:1984-1997. [PMID: 38644051 DOI: 10.1002/jor.25843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 12/15/2023] [Accepted: 03/11/2024] [Indexed: 04/23/2024]
Abstract
Immobilization-induced skeletal unloading results in muscle atrophy and rapid bone loss, thereby increasing the risk of falling and the need for implant therapy in patients with extended bed rest or neuromuscular injuries. Skeletal unloading causes bone loss by altering bone growth and resorption, suggesting that implant performance might be affected. To test this, we focused on early events in implant osseointegration. We used the rat sciatic neurectomy-induced disuse model under two different settings. In Study 1, 16 Sprague Dawley rats (SD) were separated into control, sham operated+cast immobilization, and sciatic neurectomy+casting groups; titanium implants with multiscale microtextured topography and hydrophilic chemistry (modSLA) were inserted in the distal femoral metaphysis. Neurectomy surgeries and casting were performed at the same surgical setting as implant placement; rats were euthanized 4 weeks post-implantation. In Study 2, we established the unloaded condition before implantation. A total of 12 SD rats were divided into control and sciatic+femoral neurectomy groups. A total of 24 days after sciatic and femoral neurectomy surgery, rats received implants. Study 2 rats were euthanized at 4 weeks post-implantation. MicroCT and histomorphometry showed that trabecular bone and osseointegration were reduced when disuse was established before implantation. Osteoblasts isolated from Study 1 sciatic neurectomy tibial bones exhibited impaired differentiation on modSLA culture disks, revealing a possible mechanism responsible for the decreased osseointegration observed in the Study 2 rats. This study addressed the importance of considering the mechanical unloading and muscle function history before implant insertion and suggests that implant performance was reduced due to poor cellular ability to regenerate.
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Affiliation(s)
- Jingyao Deng
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
| | - David Joshua Cohen
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Enrique B Matias
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Lucas C Olson
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Michael J McClure
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
| | - Barbara D Boyan
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
- Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Zvi Schwartz
- Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA
- Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
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Dias de Oliveira FB, Antonioli E, Dias OFM, de Souza JG, Agarwal S, Chudzinski-Tavassi AM, Ferretti M. Comparative Effects of Intra-Articular versus Intravenous Mesenchymal Stromal Cells Therapy in a Rat Model of Osteoarthritis by Destabilization of Medial Meniscus. Int J Mol Sci 2023; 24:15543. [PMID: 37958526 PMCID: PMC10649289 DOI: 10.3390/ijms242115543] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/13/2023] [Accepted: 10/16/2023] [Indexed: 11/15/2023] Open
Abstract
Transplanted mesenchymal stromal cells (MSCs) exhibit a robust anti-inflammatory and homing capacity in response to high inflammatory signals, as observed in studies focused on rheumatic diseases that target articular cartilage (AC) health. However, AC degradation in osteoarthritis (OA) does not necessarily coincide with a highly inflammatory joint profile. Often, by the time patients seek medical attention, they already have damaged AC. In this study, we examined the therapeutic potential of a single bone marrow MSC transplant (2 × 106 cells/kgbw) through two different routes: intra-articular (MSCs-IAt) and intravenous (MSCs-IVt) in a preclinical model of low-grade inflammatory OA with an established AC degeneration. OA was induced through the destabilization of the medial meniscus (DMM) in female Wistar Kyoto rats. The animals received MSCs 9 weeks after surgery and were euthanized 4 and 12 weeks post-transplant. In vivo and ex vivo tracking of MSCs were analyzed via bioluminescence and imaging flow cytometry, respectively. Cytokine/chemokine modulation in serum and synovial fluid was measured using a multiplex panel. AC degeneration was quantified through histology, and hindlimb muscle balance was assessed with precision weighing. To our knowledge, we are the first group to show the in vivo (8 h) and ex vivo (12 h) homing of cells to the DMM-OA joint following MSCs-IVt. In the case of MSCs-IAt, the detection of cellular bioluminescence at the knee joint persisted for up to 1 week. Intriguingly, intra-articular saline injection (placebo-IAt) resulted in a worse prognosis of OA when compared to a non-invasive control (placebo-IVt) without joint injection. The systemic cytokines/chemokines profile exhibited a time-dependent variation between transplant routes, displaying a transient anti-inflammatory systemic response for both MSCs-IVt and MSCs-IAt. A single injection of MSCs, whether administered via the intra-articular or intravenous route, performed 9 weeks after DMM surgery, did not effectively inhibit AC degeneration when compared to a non-invasive control.
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Affiliation(s)
| | - Eliane Antonioli
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.B.D.d.O.)
| | | | - Jean Gabriel de Souza
- Department of Biomedical Engineering, Wayne State University, Detroit, MI 48202, USA;
- CENTD Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil
| | - Sudha Agarwal
- Division of Rheumatology and Immunology, The Ohio State University College of Medicine, Columbus, OH 43210, USA
- Division of Biosciences, The Ohio State University College of Dentistry, Columbus, OH 43210, USA
| | - Ana Marisa Chudzinski-Tavassi
- CENTD Centre of Excellence in New Target Discovery, Butantan Institute, São Paulo 05503-900, Brazil
- Laboratório de Desenvolvimento e Inovação, Butantan Institute, São Paulo 05503-900, Brazil
| | - Mario Ferretti
- Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil; (F.B.D.d.O.)
- Departamento de Ortopedia e Traumatologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil
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Niu H, Wang BY, Wei XY, Wang YN, Zhu WH, Li WJ, Zhang Y, Wang JC. Anti-inflammatory therapeutic biomarkers identified of human bone marrow mesenchymal stem cell therapy on aging mice by serum proteomics and peptidomics study. J Proteomics 2023; 288:104979. [PMID: 37524227 DOI: 10.1016/j.jprot.2023.104979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 07/13/2023] [Accepted: 07/21/2023] [Indexed: 08/02/2023]
Abstract
Aging is accompanied by deterioration in physical condition, and creates high risks of diseases. Stem cell therapy exhibited promising potential in delaying aging. However, the unelucidated therapeutic mechanism limits future clinical application. Herein, to systematically understand the response to stem cell transfusion at the molecular level, we performed quantitative serum proteomic and peptidomics analyses in the 24-month-old aging mice model with or without mesenchymal stem cell (MSC) treatment. As a result, a total of 560 proteins and 2131 endogenous peptides were identified, among which, 6 proteins and 9 endogenous peptides derived from 6 precursor proteins were finally identified as therapeutic biomarkers after MSC transfusion on aging mice both by untargeted label-free quantification and targeted parallel reaction monitoring (PRM) quantification. Amazingly, the biological function of these differential proteins was mainly related to inflammation, which is not only the important hallmark of aging, but also the main cause of inducing aging. The reduction of these inflammatory protein content after MSC treatment further suggests the anti-inflammatory effect of MSC therapy reported elsewhere. Therefore, our study provides new evidence for the anti-inflammatory effect of MSC therapy for anti-aging and offers abundant data to support deeper investigations of the therapeutic mechanism of MSC in delaying aging.
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Affiliation(s)
- Huan Niu
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China
| | - Bo-Yan Wang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China
| | - Xiao-Yue Wei
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China
| | - Yan-Nan Wang
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
| | - Wen-Hui Zhu
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
| | - Wei-Jie Li
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China
| | - Ying Zhang
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China.
| | - Jian-Cheng Wang
- Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518107, China; Scientific Research Center, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518107, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou 510080, China.
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Wang C, Zhao B, Zhai J, Wang A, Cao N, Liao T, Su R, He L, Li Y, Pei X, Jia Y, Yue W. Clinical-grade human umbilical cord-derived mesenchymal stem cells improved skeletal muscle dysfunction in age-associated sarcopenia mice. Cell Death Dis 2023; 14:321. [PMID: 37173309 PMCID: PMC10182022 DOI: 10.1038/s41419-023-05843-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 04/23/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023]
Abstract
With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.
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Affiliation(s)
- Chao Wang
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Bichun Zhao
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Jinglei Zhai
- State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China
| | - Ailin Wang
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Ning Cao
- 920th Hospital of Joint Logistics Support Force, Kunming, 650032, China
| | - Tuling Liao
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
| | - Ruyu Su
- South China Institute of Biomedicine, Guangzhou, 510005, China
| | - Lijuan He
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
- South China Institute of Biomedicine, Guangzhou, 510005, China
| | - Yanhua Li
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China
- South China Institute of Biomedicine, Guangzhou, 510005, China
| | - Xuetao Pei
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
- South China Institute of Biomedicine, Guangzhou, 510005, China.
| | - Yali Jia
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
- South China Institute of Biomedicine, Guangzhou, 510005, China.
| | - Wen Yue
- Stem Cell and Regenerative Medicine Lab, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
- South China Institute of Biomedicine, Guangzhou, 510005, China.
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Rahmati M, McCarthy JJ, Malakoutinia F. Myonuclear permanence in skeletal muscle memory: a systematic review and meta-analysis of human and animal studies. J Cachexia Sarcopenia Muscle 2022; 13:2276-2297. [PMID: 35961635 PMCID: PMC9530508 DOI: 10.1002/jcsm.13043] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 05/24/2022] [Accepted: 06/13/2022] [Indexed: 12/09/2022] Open
Abstract
One aspect of skeletal muscle memory is the ability of a previously trained muscle to hypertrophy more rapidly following a period of detraining. Although the molecular basis of muscle memory remains to be fully elucidated, one potential mechanism thought to mediate muscle memory is the permanent retention of myonuclei acquired during the initial phase of hypertrophic growth. However, myonuclear permanence is debated and would benefit from a meta-analysis to clarify the current state of the field for this important aspect of skeletal muscle plasticity. The objective of this study was to perform a meta-analysis to assess the permanence of myonuclei associated with changes in physical activity and ageing. When available, the abundance of satellite cells (SCs) was also considered given their potential influence on changes in myonuclear abundance. One hundred forty-seven peer-reviewed articles were identified for inclusion across five separate meta-analyses; (1-2) human and rodent studies assessed muscle response to hypertrophy; (3-4) human and rodent studies assessed muscle response to atrophy; and (5) human studies assessed muscle response with ageing. Skeletal muscle hypertrophy was associated with higher myonuclear content that was retained in rodents, but not humans, with atrophy (SMD = -0.60, 95% CI -1.71 to 0.51, P = 0.29, and MD = 83.46, 95% CI -649.41 to 816.32, P = 0.82; respectively). Myonuclear and SC content were both lower following atrophy in humans (MD = -11, 95% CI -0.19 to -0.03, P = 0.005, and SMD = -0.49, 95% CI -0.77 to -0.22, P = 0.0005; respectively), although the response in rodents was affected by the type of muscle under consideration and the mode of atrophy. Whereas rodent myonuclei were found to be more permanent regardless of the mode of atrophy, atrophy of ≥30% was associated with a reduction in myonuclear content (SMD = -1.02, 95% CI -1.53 to -0.51, P = 0.0001). In humans, sarcopenia was accompanied by a lower myonuclear and SC content (MD = 0.47, 95% CI 0.09 to 0.85, P = 0.02, and SMD = 0.78, 95% CI 0.37-1.19, P = 0.0002; respectively). The major finding from the present meta-analysis is that myonuclei are not permanent but are lost during periods of atrophy and with ageing. These findings do not support the concept of skeletal muscle memory based on the permanence of myonuclei and suggest other mechanisms, such as epigenetics, may have a more important role in mediating this aspect of skeletal muscle plasticity.
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Affiliation(s)
- Masoud Rahmati
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human SciencesLorestan UniversityKhorramabadIran
| | - John J. McCarthy
- Department of PhysiologyUniversity of KentuckyLexingtonKYUSA
- Center for Muscle BiologyUniversity of KentuckyLexingtonKYUSA
| | - Fatemeh Malakoutinia
- Department of Physical Education and Sport Sciences, Faculty of Literature and Human SciencesLorestan UniversityKhorramabadIran
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Chen M, Wang Y, Deng S, Lian Z, Yu K. Skeletal muscle oxidative stress and inflammation in aging: Focus on antioxidant and anti-inflammatory therapy. Front Cell Dev Biol 2022; 10:964130. [PMID: 36111339 PMCID: PMC9470179 DOI: 10.3389/fcell.2022.964130] [Citation(s) in RCA: 57] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 08/10/2022] [Indexed: 12/06/2022] Open
Abstract
With aging, the progressive loss of skeletal muscle will have negative effect on multiple physiological parameters, such as exercise, respiration, thermoregulation, and metabolic homeostasis. Accumulating evidence reveals that oxidative stress and inflammation are the main pathological characteristics of skeletal muscle during aging. Here, we focus on aging-related sarcopenia, summarize the relationship between aging and sarcopenia, and elaborate on aging-mediated oxidative stress and oxidative damage in skeletal muscle and its critical role in the occurrence and development of sarcopenia. In addition, we discuss the production of excessive reactive oxygen species in aging skeletal muscle, which reduces the ability of skeletal muscle satellite cells to participate in muscle regeneration, and analyze the potential molecular mechanism of ROS-mediated mitochondrial dysfunction in aging skeletal muscle. Furthermore, we have also paid extensive attention to the possibility and potential regulatory pathways of skeletal muscle aging and oxidative stress mediate inflammation. Finally, in response to the abnormal activity of oxidative stress and inflammation during aging, we summarize several potential antioxidant and anti-inflammatory strategies for the treatment of sarcopenia, which may provide beneficial help for improving sarcopenia during aging.
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Affiliation(s)
- Mingming Chen
- College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Yiyi Wang
- Zhejiang A&F University, Zhejiang Provincial Key Laboratory of Characteristic Traditional Chinese Medicine Resources Protection and Innovative Utilization, Lin’an, China
| | - Shoulong Deng
- NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China
| | - Zhengxing Lian
- College of Animal Science and Technology, China Agricultural University, Beijing, China
- *Correspondence: Zhengxing Lian, ; Kun Yu,
| | - Kun Yu
- College of Animal Science and Technology, China Agricultural University, Beijing, China
- *Correspondence: Zhengxing Lian, ; Kun Yu,
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Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty. Int J Mol Sci 2021; 22:ijms221910542. [PMID: 34638883 PMCID: PMC8508885 DOI: 10.3390/ijms221910542] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 09/16/2021] [Accepted: 09/24/2021] [Indexed: 12/16/2022] Open
Abstract
Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients’ quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.
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Zhu Y, Ge J, Huang C, Liu H, Jiang H. Application of mesenchymal stem cell therapy for aging frailty: from mechanisms to therapeutics. Theranostics 2021; 11:5675-5685. [PMID: 33897874 PMCID: PMC8058725 DOI: 10.7150/thno.46436] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 03/15/2021] [Indexed: 12/20/2022] Open
Abstract
Aging frailty is a complex geriatric syndrome that becomes more prevalent with advancing age. It constitutes a major health problem due to frequent adverse outcomes. Frailty is characterized by disruption of physiological homeostasis and progressive decline of health status. Multiple factors contribute to development of frailty with advancing age, including genome instability, DNA damage, epigenetic alternations, stem cell exhaustion, among others. These interrelated factors comprehensively result in loss of tissue homeostasis and diminished reserve capacity in frailty. Therefore, the aged organism gradually represents symptoms of frailty with decline in physiological functions of organs. Notably, the brain, cardiovascular system, skeletal muscle, and endocrine system are intrinsically interrelated to frailty. The patients with frailty may display the diminished reserves capacity of organ systems. Due to the complex pathophysiology, no specific treatments have been approved for prevention of this syndrome. At such, effective strategies for intervening in pathogenic process to improve health status of frail patients are highly needed. Recent progress in cell-based therapy has greatly contributed to the amelioration of degenerative diseases related to age. Mesenchymal stem cells (MSCs) can exert regenerative effects and possess anti-inflammatory properties. Transplantation of MSCs represents as a promising therapeutic strategy to address the pathophysiologic problems of frail syndrome. Currently, MSC therapy have undergone the phase I and II trials in human subjects that have endorsed the safety and efficacy of MSCs for aging frailty. However, despite these positive results, caution is still needed with regard to potential to form tumors, and further large-scale studies are warranted to confirm the therapeutic efficacy of MSC therapy.
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12
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Nuge T, Liu Z, Liu X, Ang BC, Andriyana A, Metselaar HSC, Hoque ME. Recent Advances in Scaffolding from Natural-Based Polymers for Volumetric Muscle Injury. Molecules 2021; 26:699. [PMID: 33572728 PMCID: PMC7865392 DOI: 10.3390/molecules26030699] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 01/03/2021] [Accepted: 01/06/2021] [Indexed: 02/07/2023] Open
Abstract
Volumetric Muscle Loss (VML) is associated with muscle loss function and often untreated and considered part of the natural sequelae of trauma. Various types of biomaterials with different physical and properties have been developed to treat VML. However, much work remains yet to be done before the scaffolds can pass from the bench to the bedside. The present review aims to provide a comprehensive summary of the latest developments in the construction and application of natural polymers-based tissue scaffolding for volumetric muscle injury. Here, the tissue engineering approaches for treating volumetric muscle loss injury are highlighted and recent advances in cell-based therapies using various sources of stem cells are elaborated in detail. An overview of different strategies of tissue scaffolding and their efficacy on skeletal muscle cells regeneration and migration are presented. Furthermore, the present paper discusses a wide range of natural polymers with a special focus on proteins and polysaccharides that are major components of the extracellular matrices. The natural polymers are biologically active and excellently promote cell adhesion and growth. These bio-characteristics justify natural polymers as one of the most attractive options for developing scaffolds for muscle cell regeneration.
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Affiliation(s)
- Tamrin Nuge
- Department of Mechanical, Materials and Manufacturing Engineering, Faculty of Science and Engineering, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China; (T.N.); (Z.L.)
| | - Ziqian Liu
- Department of Mechanical, Materials and Manufacturing Engineering, Faculty of Science and Engineering, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China; (T.N.); (Z.L.)
| | - Xiaoling Liu
- Department of Mechanical, Materials and Manufacturing Engineering, Faculty of Science and Engineering, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo 315100, China; (T.N.); (Z.L.)
| | - Bee Chin Ang
- Centre of Advanced Materials, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.A.); (H.S.C.M.)
- Department of Chemical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Andri Andriyana
- Centre of Advanced Materials, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.A.); (H.S.C.M.)
- Department of Mechanical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Hendrik Simon Cornelis Metselaar
- Centre of Advanced Materials, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia; (A.A.); (H.S.C.M.)
- Department of Mechanical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur 50603, Malaysia
| | - Md Enamul Hoque
- Department of Biomedical Engineering, Military Institute of Science and Technology (MIST), Dhaka 1216, Bangladesh;
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13
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Abdel Latif H, Abdel Khalek R, AbdelGalil W, AbdAllah H, Fawzy A, AbdelFattah S. Nanocurcumin versus mesenchymal stem cells in ameliorating the deleterious effects in the cadmium-induced testicular injury: A crosstalk between oxidative and apoptotic markers. Andrologia 2020; 52:e13760. [PMID: 32692431 DOI: 10.1111/and.13760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 06/13/2020] [Accepted: 06/23/2020] [Indexed: 11/29/2022] Open
Abstract
Cadmium (Cd), a grave occupational pollutant, can result in; testicular damage. This study was designed to distinguish the potential effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) versus that of curcumin nanoemulsion on Cd-induced testicular damage. Fifty adult male Sprague Dawley rats were distributed into five groups; control, sham control, Cd-treated, stem cell-treated and nanocurcumin-treated groups. Histological, immune histochemical; caspase 3 and proliferating cell nuclear antigen (PCNA) and CD 68, testosterone levels, nitric oxide, malondialdehyde (MDA)/glutathione (GSH) superoxide, dismutase (SOD), Western blot; B-cell lymphoma (Bcl-2), BCL2-Associated X Protein (BAX), BAX/Bcl-2 ratio and morphometry were done. Cadmium-treated group showed degenerated, detached seminiferous tubules, vacuolations and wide interstitial spaces containing fluid exudates. The same group revealed increased expression of BAX, BAX/Bcl-2 ratio, caspase 3, CD 68 and increased mean values of MDA, NO. Concomitantly, Cd has significant reduction in PCNA, Bcl-2 and sperm cell count when compared to control group. BM-MSCs- and nanocurcumin-treated groups revealed well-structured tubules and were perceived to expressively enhance the deleterious changes induced by Cd. The injurious changes on the testis induced by Cd were obviously improved when treated with either MSCs or nano-curcumin. BM-MSCs exerted more ameliorative changes.
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Affiliation(s)
- Hany Abdel Latif
- Anatomy and Embryology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Rasha Abdel Khalek
- Anatomy and Embryology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Walid AbdelGalil
- Anatomy and Embryology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hend AbdAllah
- Anatomy and Embryology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmad Fawzy
- Medical Physiology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Shereen AbdelFattah
- Anatomy and Embryology, Kasralainy, Faculty of Medicine, Cairo University, Cairo, Egypt
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14
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Li P, Ma X, Jin W, Li X, Hu J, Jiang X, Guo X. Effects of local injection and intravenous injection of allogeneic bone marrow mesenchymal stem cells on the structure and function of damaged anal sphincter in rats. J Tissue Eng Regen Med 2020; 14:989-1000. [PMID: 32537834 DOI: 10.1002/term.3079] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 04/09/2020] [Accepted: 05/11/2020] [Indexed: 12/21/2022]
Abstract
Anal sphincter injury leads to damage to the anal structure and functions and has been identified as a major risk factor for fecal incontinence. Bone marrow mesenchymal stem cells (BMSCs) with capacities of multidifferentiation, paracrine, and low immunogenicity have been widely used in tissue repair and regeneration. The primary objective of this research was to compare the effects of different injection therapies of BMSCs on the injured anal sphincters. Ninety-six Sprague-Dawley female rats were randomly divided into four groups (n = 24 each): intravenous injection, local injection, sham operation, and normal control. For the first three groups, 25% removal of the anal sphincter complex was performed and 0.3-ml phosphate-buffered saline (PBS) (containing 107 green fluorescent protein-labeled allogeneic BMSCs) was given accordingly to the treatment group 24 h after operation for 7 consecutive days. The sham operation group was injected with 0.3-ml PBS only. All cases had undergone evaluation in the 1st, 7th, 14th, and 28th postoperative days. The rats were sacrificed on the 28th postoperative day, and the anal sphincters were dissected to be analyzed by morphological examination. At 14 days postoperatively, local injection of BMSC significantly improved the peak contraction pressure, electromyography amplitude, and frequency of the injured anal sphincter compared with tail vein, but there was no significant difference in resting pressure until 28 days after sphincterectomy. Masson staining results confirmed that the local injection group had significantly more new muscles on the wound. BMSC could remarkably improve peak contraction pressure, electromyography amplitude, and muscle fibers on the wound, and local injection is superior to intravenous injection.
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Affiliation(s)
- Peng Li
- Department of Anorectal, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoying Ma
- School of Pharmacy, East China University of Science and Technology, Shanghai, China
| | - Wenqi Jin
- Department of Anorectal, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaojia Li
- Department of Anorectal, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jie Hu
- Department of Anorectal, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Xiaoxue Jiang
- Department of Anorectal Surgery, Shanghai Eighth People's Hospital, Shanghai, China
| | - Xiutian Guo
- Department of Anorectal, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
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15
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Schwartz LM. Skeletal Muscles Do Not Undergo Apoptosis During Either Atrophy or Programmed Cell Death-Revisiting the Myonuclear Domain Hypothesis. Front Physiol 2019; 9:1887. [PMID: 30740060 PMCID: PMC6356110 DOI: 10.3389/fphys.2018.01887] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2018] [Accepted: 12/12/2018] [Indexed: 12/20/2022] Open
Abstract
Skeletal muscles are the largest cells in the body and are one of the few syncytial ones. There is a longstanding belief that a given nucleus controls a defined volume of cytoplasm, so when a muscle grows (hypertrophy) or shrinks (atrophy), the number of myonuclei change accordingly. This phenomenon is known as the “myonuclear domain hypothesis.” There is a general agreement that hypertrophy is accompanied by the addition of new nuclei from stem cells to help the muscles meet the enhanced synthetic demands of a larger cell. However, there is a considerable controversy regarding the fate of pre-existing nuclei during atrophy. Many researchers have reported that atrophy is accompanied by the dramatic loss of myonuclei via apoptosis. However, since there are many different non-muscle cell populations that reside within the tissue, these experiments cannot easily distinguish true myonuclei from those of neighboring mononuclear cells. Recently, two independent models, one from rodents and the other from insects, have demonstrated that nuclei are not lost from skeletal muscle fibers when they undergo either atrophy or programmed cell death. These and other data argue against the current interpretation of the myonuclear domain hypothesis and suggest that once a nucleus has been acquired by a muscle fiber it persists.
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Affiliation(s)
- Lawrence M Schwartz
- Department of Biology, Morrill Science Center, University of Massachusetts, Amherst, MA, United States
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16
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Wang QQ, Jing XM, Bi YZ, Cao XF, Wang YZ, Li YX, Qiao BJ, Chen Y, Hao YL, Hu J. Human Umbilical Cord Wharton's Jelly Derived Mesenchymal Stromal Cells May Attenuate Sarcopenia in Aged Mice Induced by Hindlimb Suspension. Med Sci Monit 2018; 24:9272-9281. [PMID: 30571669 PMCID: PMC6320659 DOI: 10.12659/msm.913362] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background Since the use of human umbilical cord Wharton’s Jelly derived mesenchymal stromal cells (hWJ-MSCs) to treat sarcopenia has not been explored, we studied the effects of hWJ-MSCs in aged male C57BL/6J mice with sarcopenia induced by hindlimb suspension, and explored the potential mechanism. Material/Methods Hindlimb suspension was used to induce sarcopenia in 24-month-old C57BL/6J mice and green fluorescent protein-tagged hWJ-MSCs and controls were transplanted into mice via tail vein or local intramuscular injection. After hWJ-MSC transplantation, changes in whole body muscle strength and endurance, gastrocnemius muscle weight and myofiber cross-sectional area (CSA) were studied. Proliferation of skeletal muscle stem cell, apoptosis, and chronic inflammation were also investigated. Results We demonstrated that whole body muscle strength and endurance, gastrocnemius muscle mass, and CSA were significantly increased in hWJ-MSC-transplanted mice than in controls (P<0.05). In hWJ-MSC-transplanted mice, apoptotic myonuclei was reduced, and BrdU and Pax-7 expression indices of gastrocnemius muscles were increased (P<0.05). Tumor necrosis factor (TNF)-α and interleukin (IL)-6 were downregulated, and IL-4 and IL-10 were upregulated (P<0.05). Conclusions hWJ-MSCs may ameliorate sarcopenia in aged male C57BL/6J mice induced by hindlimb suspension, and this may be via activation of resident skeletal muscle satellite cells, reduction of apoptosis, and less chronic inflammation.
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Affiliation(s)
- Quan-Quan Wang
- Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland).,Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Xiao-Ma Jing
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland)
| | - Yan-Zhen Bi
- Difficult and Complicated Liver Diseases and Artificial Liver Center, Beijing YouAn Hospital, Capital Medical University, Beijing, China (mainland)
| | - Xiao-Fu Cao
- Department of Pharmacy, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Yu-Zhong Wang
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Yan-Xin Li
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China (mainland)
| | - Bao-Jun Qiao
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Yun Chen
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Yan-Lei Hao
- Department of Neurology, Affiliated Hospital of Jining Medical University, Jining, Shandong, China (mainland)
| | - Jing Hu
- Department of Neuromuscular Disorders, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China (mainland)
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17
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Koide M, Hagiwara Y, Tsuchiya M, Kanzaki M, Hatakeyama H, Tanaka Y, Minowa T, Takemura T, Ando A, Sekiguchi T, Yabe Y, Itoi E. Retained Myogenic Potency of Human Satellite Cells from Torn Rotator Cuff Muscles Despite Fatty Infiltration. TOHOKU J EXP MED 2018; 244:15-24. [PMID: 29311489 DOI: 10.1620/tjem.244.15] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
Rotator cuff tears (RCTs) are a common shoulder problem in the elderly that can lead to both muscle atrophy and fatty infiltration due to less physical load. Satellite cells, quiescent cells under the basal lamina of skeletal muscle fibers, play a major role in muscle regeneration. However, the myogenic potency of human satellite cells in muscles with fatty infiltration is unclear due to the difficulty in isolating from small samples, and the mechanism of the progression of fatty infiltration has not been elucidated. The purpose of this study was to analyze the population of myogenic and adipogenic cells in disused supraspinatus (SSP) and intact subscapularis (SSC) muscles of the RCTs from the same patients using fluorescence-activated cell sorting. The microstructure of the muscle with fatty infiltration was observed as a whole mount condition under multi-photon microscopy. Myogenic differentiation potential and gene expression were evaluated in satellite cells. The results showed that the SSP muscle with greater fatty infiltration surrounded by collagen fibers compared with the SSC muscle under multi-photon microscopy. A positive correlation was observed between the ratio of muscle volume to fat volume and the ratio of myogenic precursor to adipogenic precursor. Although no difference was observed in the myogenic potential between the two groups in cell culture, satellite cells in the disused SSP muscle showed higher intrinsic myogenic gene expression than those in the intact SSC muscle. Our results indicate that satellite cells from the disused SSP retain sufficient potential of muscle growth despite the fatty infiltration.
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Affiliation(s)
- Masashi Koide
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
| | - Yoshihiro Hagiwara
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
| | | | - Makoto Kanzaki
- Graduate School of Biomedical Engineering, Tohoku University
| | - Hiroyasu Hatakeyama
- Graduate School of Biomedical Engineering, Tohoku University.,Frontier Research Institute for Interdisciplinary Sciences, Tohoku University
| | - Yukinori Tanaka
- Department of Oral Immunology, Tohoku University Graduate School of Dentistry
| | | | | | - Akira Ando
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
| | - Takuya Sekiguchi
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
| | - Yutaka Yabe
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
| | - Eiji Itoi
- Department of Orthopaedic Surgery, Tohoku University Graduate School of Medicine
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