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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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Glotzbach K, Stamm N, Weberskirch R, Faissner A. Cationic Hydrogels Modulate Neural Stem and Progenitor Cell Proliferation and Differentiation Behavior in Dependence of Cationic Moiety Concentration in 2D Cell Culture. ACS Biomater Sci Eng 2024; 10:3148-3163. [PMID: 38227432 DOI: 10.1021/acsbiomaterials.3c01668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2024]
Abstract
The central nervous system (CNS) has a limited regenerative capacity because a hostile environment prevents tissue regeneration after damage or injury. Neural stem/progenitor cells (NSPCs) are considered a potential resource for CNS repair, which raises the issue of adequate cultivation and expansion procedures. Cationic charge supports the survival and adhesion of NSPCs. Typically, tissue culture plates with cationic coatings, such as poly-l-ornithine (PLO), have been used to culture these cell types (NSPCs). Yet presently, little is known about the impact of cationic charge concentration on the viability, proliferation, and differentiation capacity of NSPCs. Therefore, we have recently developed well-defined, fully synthetic hydrogel systems G1 (gel 1) to G6 (gel 6) that allow for the precise control of the concentration of the cationic trimethylaminoethyl acrylate (TMAEA) molecule associated with the polymer in a range from 0.06 to 0.91 μmol/mg. When murine NSPCs were cultured on these gels under differentiation conditions, we observed a strong correlation of cationic charge concentration with NSPC survival. In particular, neurons were preferentially formed on gels with a higher cationic charge concentration, whereas astrocytes and oligodendrocytes favored weakly charged or even neutral gel surfaces. To test the properties of the gels under proliferative conditions, the NSPCs were cultivated in the presence of fibroblast growth factor 2 (FGF2). The cytokine significantly increased the number of NSPCs but delayed the differentiation toward neurons and glia cells. Thus, the hydrogels are compatible with the survival, expansion, and differentiation of NSPCs and may be useful to create supportive environments in transplantation approaches.
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Affiliation(s)
- Kristin Glotzbach
- Department of Cell Morphology and Molecular Neurobiology, Ruhr Universität Bochum, Bochum 44801, Germany
| | - Nils Stamm
- Department of Chemistry and Chemical Biology, TU Dortmund University, Dortmund 44227, Germany
| | - Ralf Weberskirch
- Department of Chemistry and Chemical Biology, TU Dortmund University, Dortmund 44227, Germany
| | - Andreas Faissner
- Department of Cell Morphology and Molecular Neurobiology, Ruhr Universität Bochum, Bochum 44801, Germany
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Wen J, Liu L, Li J, He Y. A review of nardosinone for pharmacological activities. Eur J Pharmacol 2021; 908:174343. [PMID: 34265296 DOI: 10.1016/j.ejphar.2021.174343] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/16/2021] [Accepted: 07/11/2021] [Indexed: 11/20/2022]
Abstract
Nardostachys jatamansi is a natural medicinal plant that is widely used in Asia for the treatment of various neurological and cardiac diseases, and nardosinone is the main active ingredient of N. jatamansi, which has the potential to treat a variety of diseases. Herein, we summarize the reported chemical structure, pharmacokinetics and pharmacological potential of nardosinone, and point out areas for further research. We obtained studies that were related to the chemical structure and pharmacological activities of nardosinone from several databases. Previous studies have shown that nardosinone has anti-inflammatory effects, anti-hypertrophic effect in cardiomyocytes, enhances activity of the nerve growth factor and promotes neural stem cells to proliferate and differentiate. However, the molecular mechanism of how nardosinone promotes proliferation and differentiation of neural stem cells, and its role in resisting cardiomyocyte hypertrophy remains unclear and needs to be further studied. Overall, nardosinone has the potential to treat bacterial infections, periodontitis, cardiac diseases, neurodegenerative diseases and cancer. However, the gaps found in the literature is the lack of more comprehensive information regarding the pharmacokinetics and toxicology of nardosinone.
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Affiliation(s)
- Jiawei Wen
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Linqiu Liu
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Junjun Li
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China
| | - Yang He
- State Key Laboratory of Southwestern Chinese Medicine Resources, College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 611137, China.
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Rzepnikowska W, Kochański A. Models for IGHMBP2-associated diseases: an overview and a roadmap for the future. Neuromuscul Disord 2021; 31:1266-1278. [PMID: 34785121 DOI: 10.1016/j.nmd.2021.08.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 07/16/2021] [Accepted: 08/06/2021] [Indexed: 12/13/2022]
Abstract
Models are practical tools with which to establish the basic aspects of a diseases. They allow systematic research into the significance of mutations, of cellular and molecular pathomechanisms, of therapeutic options and of functions of diseases associated proteins. Thus, disease models are an integral part of the study of enigmatic proteins such as immunoglobulin mu-binding protein 2 (IGHMBP2). IGHMBP2 has been well defined as a helicase, however there is little known about its role in cellular processes. Notably, it is unclear why changes in such an abundant protein lead to specific neuronal disorders including spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Charcot-Marie-Tooth type 2S (CMT2S). SMARD1 is caused by a loss of motor neurons in the spinal cord that results in muscle atrophy and is accompanied by rapid respiratory failure. In contrast, CMT2S manifests as a severe neuropathy, but typically without critical breathing problems. Here, we present the clinical manifestation of IGHMBP2 mutations, function of protein and models that may be used for the study of IGHMBP2-associated disorders. We highlight the strengths and weaknesses of specific models and discuss the orthologs of IGHMBP2 that are found in different systems with regard to their similarity to human IGHMBP2.
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Affiliation(s)
- Weronika Rzepnikowska
- Neuromuscular Unit, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw 02-106, Poland.
| | - Andrzej Kochański
- Neuromuscular Unit, Mossakowski Medical Research Institute Polish Academy of Sciences, Warsaw 02-106, Poland
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Inhibiting PDE7A Enhances the Protective Effects of Neural Stem Cells on Neurodegeneration and Memory Deficits in Sevoflurane-Exposed Mice. eNeuro 2021; 8:ENEURO.0071-21.2021. [PMID: 34135002 PMCID: PMC8266220 DOI: 10.1523/eneuro.0071-21.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 05/21/2021] [Accepted: 05/25/2021] [Indexed: 12/03/2022] Open
Abstract
Sevoflurane is widely used in general anesthesia, especially for children. However, prolonged exposure to sevoflurane is reported to be associated with adverse effects on the development of brain in infant monkey. Neural stem cells (NSCs), with potent proliferation, differentiation, and renewing ability, provide an encouraging tool for basic research and clinical therapies for neurodegenerative diseases. We aim to explore the functional effects of injecting NSCs with phosphodiesterase 7A (PDE7A) knock-down in infant mice exposed to sevoflurane. The effects of PDE7A in NSCs proliferation and differentiation were determined by cell counting kit-8 (CCK-8) assay and differentiation-related gene expression assay, respectively. The effects of NSCs with modified PDE7A on mice’s long-term memory and learning ability were assessed by behavioral assays. Our data demonstrated that depleting PDE7A promoted, whereas forcing PDE7A suppressed the activation of cAMP/cAMP-response element binding protein (CREB) signaling as well as cell proliferation and neuronal differentiation of NSCs. Inhibition of PDE7A in NSCs exhibited profound improved effects on long-term memory and learning ability of mice exposed to sevoflurane. Our results for the first time show that knock-down of PDE7A improves the neurogenesis of NSCs in vitro and in vivo, and is beneficial for alleviating sevoflurane-induced brain damage in infant mice.
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Borziak K, Parvanova I, Finkelstein J. ReMeDy: a platform for integrating and sharing published stem cell research data with a focus on iPSC trials. Database (Oxford) 2021; 2021:baab038. [PMID: 34156448 PMCID: PMC8218701 DOI: 10.1093/database/baab038] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 05/25/2021] [Accepted: 05/28/2021] [Indexed: 12/28/2022]
Abstract
ABSTRACT Recent regenerative medicine studies have emphasized the need for increased standardization, harmonization and sharing of information related to stem cell product characterization, to help drive these innovative interventions toward public availability and to increase collaboration in the scientific community. Although numerous attempts and numerous databases have been made to manage these data, a platform that incorporates all the heterogeneous data collected from stem cell projects into a harmonized project-based framework is still lacking. The aim of the database, which is described in this study, is to provide an intelligent informatics solution that integrates comprehensive characterization of diverse stem cell product characteristics with research subject and project outcome information. In the resulting platform, heterogeneous data are validated using predefined ontologies and stored in a relational database, to ensure data quality and ease of access. Testing was performed using 51 published, publically available induced pluripotent stem cell projects conducted in clinical, preclinical and in-vitro evaluations. Future aims of this project include further increasing the database size to include all published stem cell trials and develop additional data visualization tools to improve usability. Our testing demonstrated the robustness of the proposed platform, by seamlessly harmonizing diverse common data elements, and the potential of this platform for driving knowledge generation from the aggregation and harmonization of these diverse data. DATABASE URL https://remedy.mssm.edu/.
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Affiliation(s)
- Kirill Borziak
- Center for Biomedical and Population Health Informatics, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn L2-36, New York, NY 10029, USA
| | - Irena Parvanova
- Center for Biomedical and Population Health Informatics, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn L2-36, New York, NY 10029, USA
| | - Joseph Finkelstein
- Center for Biomedical and Population Health Informatics, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Icahn L2-36, New York, NY 10029, USA
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De Gioia R, Biella F, Citterio G, Rizzo F, Abati E, Nizzardo M, Bresolin N, Comi GP, Corti S. Neural Stem Cell Transplantation for Neurodegenerative Diseases. Int J Mol Sci 2020; 21:E3103. [PMID: 32354178 PMCID: PMC7247151 DOI: 10.3390/ijms21093103] [Citation(s) in RCA: 150] [Impact Index Per Article: 30.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 04/24/2020] [Accepted: 04/27/2020] [Indexed: 01/19/2023] Open
Abstract
Neurodegenerative diseases are disabling and fatal neurological disorders that currently lack effective treatment. Neural stem cell (NSC) transplantation has been studied as a potential therapeutic approach and appears to exert a beneficial effect against neurodegeneration via different mechanisms, such as the production of neurotrophic factors, decreased neuroinflammation, enhanced neuronal plasticity and cell replacement. Thus, NSC transplantation may represent an effective therapeutic strategy. To exploit NSCs' potential, some of their essential biological characteristics must be thoroughly investigated, including the specific markers for NSC subpopulations, to allow profiling and selection. Another key feature is their secretome, which is responsible for the regulation of intercellular communication, neuroprotection, and immunomodulation. In addition, NSCs must properly migrate into the central nervous system (CNS) and integrate into host neuronal circuits, enhancing neuroplasticity. Understanding and modulating these aspects can allow us to further exploit the therapeutic potential of NSCs. Recent progress in gene editing and cellular engineering techniques has opened up the possibility of modifying NSCs to express select candidate molecules to further enhance their therapeutic effects. This review summarizes current knowledge regarding these aspects, promoting the development of stem cell therapies that could be applied safely and effectively in clinical settings.
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Affiliation(s)
- Roberta De Gioia
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Fabio Biella
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Gaia Citterio
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Federica Rizzo
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Elena Abati
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Monica Nizzardo
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Nereo Bresolin
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
| | - Giacomo Pietro Comi
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neuromuscular and Rare Diseases Unit, Via Francesco Sforza 35, 20122 Milan, Italy
| | - Stefania Corti
- Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122 Milan, Italy
- Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, 20122 Milan, Italy
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Zumwalt M, Reddy AP. Stem Cells for Treatment of Musculoskeletal Conditions - Orthopaedic/Sports Medicine Applications. Biochim Biophys Acta Mol Basis Dis 2020; 1866:165624. [PMID: 31794866 DOI: 10.1016/j.bbadis.2019.165624] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2019] [Revised: 11/22/2019] [Accepted: 11/23/2019] [Indexed: 12/20/2022]
Abstract
A myriad of musculoskeletal conditions afflicts a vast number of the world's population from birth to death. Countless pathological diseases and traumatic injuries (acute and chronic) contribute to different human disabilities, causing a tremendous financial toll on the economy of healthcare. The medical field is continually searching for novel ways to combat orthopedically related conditions. The immediate goal is the restoration of anatomy then ultimately return of function in hopes of enhancing quality if not the quantity of life. Traditional methods involve surgical correction/reconstruction of skeletal deformities from fractures/soft tissue damage/ruptures or replacement/resection of degenerated joints. Modern research is currently concentrating on innovative procedures to replenish/restore the human body close to its original/natural state [1, 2].
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Affiliation(s)
- Mimi Zumwalt
- Texas Tech University Health Sciences Center, Department of Orthopaedic Surgery, 3601 4(th) Street STOP 9436, Lubbock, TX 79430 United States of America.
| | - Arubala P Reddy
- Texas Tech University, 1301 Akron Avenue, Lubbock, TX 79409 United States of America.
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