Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Anatomy, Fujita Health University, Toyoake, Aichi, Japan; AMED-CREST, AMED, 1-7-1 Otemachi, Chiyoda, Tokyo, Japan.
Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Department of Biomedical Engineering, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Japan.
Stem Cell Reports. 2019 Aug 13;13(2):352-365. doi: 10.1016/j.stemcr.2019.06.006. Epub 2019 Jul 25.
The use of adult skeletal muscle stem cells (MuSCs) for cell therapy has been attempted for decades, but still encounters considerable difficulties. MuSCs derived from human induced pluripotent stem cells (hiPSCs) are promising candidates for stem cell therapy to treat Duchenne muscular dystrophy (DMD). Here we report that four transcription factors, HEYL, KLF4, MYOD, and PAX3, selected by comprehensive screening of different MuSC populations, enhance the derivation of PAX3-positive myogenic progenitors from fibroblasts and hiPSCs, using medium that promotes the formation of presomitic mesoderm. These induced PAX3-positive cells contribute efficiently to the repair of DMD-damaged myofibers and also reconstitute the MuSC population. These studies demonstrate how a combination of core transcription factors can fine-tune the derivation of MuSCs capable of contributing to the repair of adult skeletal muscle.
几十年来，人们一直试图利用成体骨骼肌干细胞（MuSCs）进行细胞治疗，但仍面临相当大的困难。从人诱导多能干细胞（hiPSCs）中分离得到的 MuSCs 是治疗杜氏肌营养不良症（DMD）的干细胞治疗有希望的候选物。在这里，我们报告了通过对不同 MuSC 群体的综合筛选选择的四个转录因子 HEYL、KLF4、MYOD 和 PAX3，使用促进体节中胚层形成的培养基，可增强从成纤维细胞和 hiPSCs 中衍生出 PAX3 阳性的成肌祖细胞。这些诱导的 PAX3 阳性细胞有效地有助于修复 DMD 损伤的肌纤维，并且还重建 MuSC 群体。这些研究表明，核心转录因子的组合如何精细调节 MuSCs 的衍生，使其能够有助于修复成人骨骼肌。
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