Hodgson B, Mafi R, Mafi P
Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, United Kingdom.
St Andrew's Centre for Plastic Surgery and Burns, Broomfield Hospital, Chelmsford, CM1 7ET, United Kingdom.
Curr Stem Cell Res Ther. 2018;13(5):384-407. doi: 10.2174/1574888X11666170907113151.
Mesenchymal Stem Cells (MSCs) are an attractive option for the development of treatment for musculoskeletal pathologies due to their wide availability, clinical safety and multiple techniques available. Understanding the control of MSC differentiation into skeletal muscle is vital for developing protocols and therapeutic applications that are safe and effective. This paper therefore aims to review the current understanding of factors that regulate the differentiation of MSCs into skeletal muscle. Medline, Embase, Pubmed and Web of Science were searched for December 2015 using the terms 'differentia*, skeletal*, skeleton*, myocyt*, myogen* and mesenchym* stem-cell*. This returned a total of 1215 results. 48 papers were included in the review. Forty-eight studies were reviewed. Eight related to external signalling molecules, sixteen related to local environmental factors and twenty-four related to intracellular signalling pathways. Uniaxial strain, medium stiffness of the extracellular matrix and submicron grooved topography were identified as promoting myogenesis. TGF-β was identified as a main inhibitor of myogenesis. Smad and Pax signalling were identified as important intracellular pathways and the relationship of menin, Setdb1, GEFT, PAX3-FOXO1, IGF-II, TAZ and PRDM2 with MyoD and MyoG was explored. Further research into the effect of the inflammatory response on skeletal muscle differentiation is suggested. Clarification of the mechanism of action of TGF-β, the role of submicron grooves and cyclic uniaxial strain, and two important factors in the development of tissue scaffolds.
间充质干细胞（MSCs）因其广泛的可获取性、临床安全性以及多种可用技术，成为开发肌肉骨骼疾病治疗方法的一个有吸引力的选择。了解MSCs向骨骼肌分化的调控机制对于制定安全有效的方案和治疗应用至关重要。因此，本文旨在综述目前对调控MSCs向骨骼肌分化的因素的理解。2015年12月，使用“differentia*、skeletal*、skeleton*、myocyt*、myogen和mesenchym stem-cell*”等术语在Medline、Embase、Pubmed和Web of Science数据库中进行检索。共检索到1215条结果。本综述纳入了48篇论文。对48项研究进行了综述。其中8项与外部信号分子有关，16项与局部环境因素有关，24项与细胞内信号通路有关。单轴应变、细胞外基质的中等硬度和亚微米级带凹槽的表面形貌被确定为促进肌生成的因素。转化生长因子-β（TGF-β）被确定为肌生成的主要抑制剂。Smad和Pax信号通路被确定为重要的细胞内信号通路，并探讨了Menin、Setdb1、GEFT、PAX3-FOXO1、胰岛素样生长因子-II（IGF-II）、转录共激活因子TAZ和PRDM2与肌分化蛋白D（MyoD）和肌细胞生成素（MyoG）的关系。建议进一步研究炎症反应对骨骼肌分化的影响。阐明TGF-β的作用机制、亚微米级凹槽和循环单轴应变的作用以及组织支架开发中的两个重要因素。
