Human pluripotent stem cell (hPSC)-derived myogenic progenitor cell (MPC) transplantation is a promising therapeutic approach for a variety of degenerative muscle disorders. Here, using an MPC-specific fluorescent reporter system (PAX7::GFP), we demonstrate that hPSC-derived MPCs can contribute to the regeneration of myofibers in mice following local injury and in mice deficient of dystrophin (mdx). We also demonstrate that a subset of PAX7::GFP MPCs engraft within the basal lamina of regenerated myofibers, adopt a quiescent state, and contribute to regeneration upon reinjury and in mdx mouse models. This subset of PAX7::GFP MPCs undergo a maturation process and remodel their molecular characteristics to resemble those of late-stage fetal MPCs/adult satellite cells following in vivo engraftment. These in-vivo-matured PAX7::GFP MPCs retain a cell-autonomous ability to regenerate and can repopulate in the niche of secondary recipient mice, providing a proof of principle for future hPSC-based cell therapy for muscle disorders.

人多能干细胞 (hPSC) 衍生的肌源性祖细胞 (MPC) 移植是一种很有前景的治疗各种退行性肌肉疾病的方法。在这里，使用 MPC 特异性荧光报告系统 (PAX7::GFP)，我们证明 hPSC 衍生的 MPC 可以促进局部损伤后小鼠和缺乏抗肌萎缩蛋白 ( mdx )的小鼠的肌纤维再生。我们还证明了 PAX7::GFP MPC 的一个子集植入再生肌纤维的基底层内，采用静止状态，并有助于在再损伤和mdx小鼠模型中的再生。PAX7::GFP MPCs 的这个子集经历了一个成熟过程并重塑了它们的分子特征，使其类似于晚期胎儿 MPCs/成体卫星细胞体内植入。这些体内成熟的 PAX7::GFP MPC 保留了细胞自主再生能力，并且可以在二次受体小鼠的生态位中重新繁殖，为未来基于 hPSC 的肌肉疾病细胞疗法提供了原理证明。