Owston Heather, Giannoudis Peter V, Jones Elena
Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK; Institute of Medical and Biological Engineering, Faculty of Mechanical Engineering, University of Leeds, Leeds, UK.
Leeds Institute of Rheumatic and Musculoskeletal Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Unit, Chapel Allerton Hospital, LS7 4SA Leeds, West Yorkshire, Leeds, UK.
Injury. 2016 Dec;47 Suppl 6:S3-S15. doi: 10.1016/S0020-1383(16)30834-8.
Mesenchymal stem cells (MSC) from bone marrow and periosteum are known to be heavily involved in fracture repair and bone regeneration is thought to be impaired when the surrounding skeletal muscle is damaged. Recent literature from mouse in vivo models suggest that cells originating from skeletal muscle can occupy a fracture callus during open fracture repair when periosteum is compromised. This systematic review set out to ascertain whether there are MSCs residing in human skeletal muscle and whether cells from human skeletal muscle are capable of forming bone in vitro and in vivo. Original journal articles were selected if they included the terms "skeletal muscle" and "mesenchymal" and used human skeletal muscle samples. Between January 2005 and September 2016, 1000 articles were screened of which, 16 studies met the inclusion criteria for this review. Human skeletal muscle derived cells (SMDC) had the MSC phenotype, positive for CD73, CD90 and CD105 and negative for CD34 and CD45 as well as the potential to differentiate into osteoblasts, chondrocytes and adipocytes in vitro. In addition, SMDC could form bone in vivo when seeded onto an osteoinductive scaffold. A subset of SMDC expressing a pericyte marker (PDGFRα) also expressed the MSC phenotype and were more osteogenic in vivo in comparison to SMDC expressing a satellite cell marker (CD56). The studies included were limited through variation of SMDC extraction methods and tissue culture conditions, which causes heterogeneuous cell cultures. Also, in vitro differentiation assays were not always carried out with bone marrow MSC positive controls. Current evidence suggests that cells with the MSC phenotype reside within human skeletal muscle and are capable of in vivo bone formation in combination with osteoinductive bone scaffolds. This has implications of future development of guided bone regeneration strategies to enhance large bone defect repair, whereby more thought into whether the fracture site should be "blocked" from the skeletal muscle should be carried out.
已知来自骨髓和骨膜的间充质干细胞（MSC）在骨折修复中发挥重要作用，并且当周围骨骼肌受损时，骨再生被认为会受到损害。来自小鼠体内模型的最新文献表明，在开放性骨折修复过程中，当骨膜受损时，源自骨骼肌的细胞可占据骨折痂。本系统评价旨在确定人类骨骼肌中是否存在MSC，以及来自人类骨骼肌的细胞是否能够在体外和体内形成骨。如果原始期刊文章包含“骨骼肌”和“间充质”等术语并使用人类骨骼肌样本，则将其纳入。在2005年1月至2016年9月期间，共筛选了1000篇文章，其中16项研究符合本评价的纳入标准。人类骨骼肌衍生细胞（SMDC）具有MSC表型，CD73、CD90和CD105呈阳性，CD34和CD45呈阴性，并且在体外具有分化为成骨细胞、软骨细胞和脂肪细胞的潜力。此外，当接种到骨诱导支架上时，SMDC可在体内形成骨。表达周细胞标志物（PDGFRα）的一部分SMDC也表达MSC表型，与表达卫星细胞标志物（CD56）的SMDC相比，在体内具有更强的成骨能力。纳入的研究存在局限性，因为SMDC提取方法和组织培养条件存在差异，这导致细胞培养存在异质性。此外，体外分化试验并非总是与骨髓MSC阳性对照一起进行。目前的证据表明，具有MSC表型的细胞存在于人类骨骼肌中，并且能够与骨诱导骨支架结合在体内形成骨。这对引导骨再生策略的未来发展具有启示意义，以增强大骨缺损修复，因此应更多地考虑骨折部位是否应与骨骼肌“隔离”。
