Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model
Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model
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DOI：
10.1016/j.stemcr.2020.06.004
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发表时间：
2020-07-14
影响因子：
5.9
通讯作者：
Sakurai, Hidetoshi
中科院分区：
文献类型：
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作者：
Zhao, Mingming;Tazumi, Atsutoshi;Sakurai, Hidetoshi
杜氏肌营养不良症（DMD）是一种由肌营养不良蛋白缺乏引起的进行性和致命性肌肉萎缩疾病。使用肌肉干细胞（MuSCs）进行细胞治疗是一种潜在的治疗方法。在这里，我们报告了一种通过监测MYF5表达从人诱导多能干细胞（iPSCs）分化生成胎儿musc的方法。基因表达谱显示myf5阳性细胞在分化后期具有胎儿MuSC特征，而myf5阳性细胞在分化早期具有早期肌源性祖细胞特征。此外，晚期myf5阳性细胞移植到DMD模型小鼠体内后，表现出良好的肌肉再生潜力，并在体内产生DYSTROPHIN，使肌肉功能恢复。移植物细胞在dystrophin阳性纤维基底层下也产生pax7阳性的musc样细胞。这些发现表明，在iPSC分化后期诱导的myf5阳性胎儿musc具有治疗DMD的细胞潜力。
Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle-wasting disease caused by DYSTROPHIN deficiency. Cell therapy using muscle stem cells (MuSCs) is a potential cure. Here, we report a differentiation method to generate fetal MuSCs from human induced pluripotent stem cells (iPSCs) by monitoring MYF5 expression. Gene expression profiling indicated that MYF5-positive cells in the late stage of differentiation have fetal MuSC characteristics, while MYF5-positive cells in the early stage of differentiation have early myogenic progenitor characteristics. Moreover, late-stage MYF5-positive cells demonstrated good muscle regeneration potential and pro-duced DYSTROPHIN in vivo after transplantation into DMD model mice, resulting in muscle function recovery. The engrafted cells also generated PAX7-positive MuSC-like cells under the basal lamina of DYSTROPHIN-positive fibers. These findings suggest that MYF5-pos- itive fetal MuSCs induced in the late stage of iPSC differentiation have cell therapy potential for DMD.