Stem Cell Research Center, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Bridgeside Point II, Suite 206, 450 Technology Drive, Pittsburgh, Pennsylvania 15219, USA.
J Orthop Res. 2013 Jul;31(7):1089-95. doi: 10.1002/jor.22335. Epub 2013 Apr 1.
We have previously reported the high regenerative potential of murine muscle-derived stem cells (mMDSCs) that are capable of differentiating into multiple mesodermal cell lineages, including myogenic, endothelial, chondrocytic, and osteoblastic cells. Recently, we described a putative human counterpart of mMDSCs, the myogenic endothelial cells (MECs), in adult human skeletal muscle, which efficiently repair/regenerate the injured and dystrophic skeletal muscle as well as the ischemic heart in animal disease models. Nevertheless it remained unclear whether human MECs, at the clonal level, preserve mMDSC-like chondrogenic and osteogenic potentials and classic stem cell characteristics including high proliferation and resistance to stress. Herein, we demonstrated that MECs, sorted from fresh postnatal human skeletal muscle biopsies, can be grown clonally and exhibit robust resistance to oxidative stress with no tumorigeneity. MEC clones were capable of differentiating into chondrocytes and osteoblasts under inductive conditions in vitro and participated in cartilage and bone formation in vivo. Additionally, adipogenic and angiogenic potentials of clonal MECs (cMECs) were observed. Overall, our study showed that cMECs not only display typical properties of adult stem cells but also exhibit chondrogenic and osteogenic capacities in vitro and in vivo, suggesting their potential applications in articular cartilage and bone repair/regeneration.
我们之前曾报道过，小鼠肌肉来源的干细胞（mMDSCs）具有很强的再生能力，能够分化为多种中胚层细胞谱系，包括肌源性、内皮细胞、软骨细胞和成骨细胞。最近，我们在成人骨骼肌中描述了一种假定的人类 mMDSC 同源物，即肌内皮细胞（MECs），它在动物疾病模型中能有效地修复/再生受损和萎缩的骨骼肌以及缺血性心脏。然而，仍不清楚人类 MECs 在克隆水平上是否具有类似于 mMDSC 的软骨和成骨潜能以及经典的干细胞特征，包括高增殖和抗应激能力。在此，我们证明了从新鲜的出生后人类骨骼肌活检中分离出来的 MEC 可以进行克隆培养，并具有很强的抗氧化应激能力，且无致瘤性。MEC 克隆在体外诱导条件下能够分化为软骨细胞和成骨细胞，并参与体内软骨和骨的形成。此外，还观察到克隆 MEC（cMEC）的成脂和成血管潜能。总的来说，我们的研究表明，cMECs 不仅显示出成年干细胞的典型特性，而且在体外和体内具有软骨和成骨能力，这表明它们在关节软骨和骨修复/再生方面具有潜在的应用前景。
