Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Clinical Application, Center for iPS Cell Research and Application (CiRA), Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
Stem Cell Reports. 2021 Apr 13;16(4):883-898. doi: 10.1016/j.stemcr.2021.03.004. Epub 2021 Apr 1.
The transplantation of muscle progenitor cells (MuPCs) differentiated from human induced pluripotent stem cells (hiPSCs) is a promising approach for treating skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). However, proper purification of the MuPCs before transplantation is essential for clinical application. Here, by using MYF5 hiPSC reporter lines, we identified two markers for myogenic cell purification: CDH13, which purified most of the myogenic cells, and FGFR4, which purified a subset of MuPCs. Cells purified with each of the markers showed high efficiency for regeneration after transplantation and contributed to the restoration of dystrophin expression in DMD-immunodeficient model mice. Moreover, we found that MYF5 regulates CDH13 expression by binding to the promoter regions. These findings suggest that FGFR4 and CDH13 are strong candidates for the purification of hiPSC-derived MuPCs for therapeutical application.
将人类诱导多能干细胞(hiPSCs)分化而来的肌肉祖细胞(MuPCs)移植是治疗杜氏肌营养不良症(DMD)等骨骼肌疾病的一种很有前途的方法。然而,在移植前对 MuPCs 进行适当的纯化对于临床应用至关重要。在这里,我们通过使用 MYF5 hiPSC 报告系,鉴定了两种用于肌细胞纯化的标记物:CDH13,它能纯化大部分的肌细胞,和 FGFR4,它能纯化 MuPCs 的一个亚群。用每种标记物纯化的细胞在移植后显示出高效的再生能力,并有助于恢复 DMD 免疫缺陷模型小鼠中的肌营养不良蛋白表达。此外,我们发现 MYF5 通过结合启动子区域来调节 CDH13 的表达。这些发现表明,FGFR4 和 CDH13 是用于治疗应用的 hiPSC 衍生 MuPCs 纯化的有力候选物。