Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Cells. 2023 Jan 18;12(3):362. doi: 10.3390/cells12030362.
Differentiation of pluripotent stem cells (PSCs) is a promising approach to obtaining large quantities of skeletal myogenic progenitors for disease modeling and cell-based therapy. However, generating skeletal myogenic cells with high regenerative potential is still challenging. We recently reported that skeletal myogenic progenitors generated from mouse PSC-derived teratomas possess robust regenerative potency. We have also found that teratomas derived from human PSCs contain a skeletal myogenic population. Here, we showed that these human PSC-derived skeletal myogenic progenitors had exceptional engraftability. A combination of cell surface markers, CD82, ERBB3, and NGFR enabled efficient purification of skeletal myogenic progenitors. These cells expressed PAX7 and were able to differentiate into MHC+ multinucleated myotubes. We further discovered that these cells are expandable in vitro. Upon transplantation, the expanded cells formed new dystrophin fibers that reconstituted almost ¾ of the total muscle volume, and repopulated the muscle stem cell pool. Our study, therefore, demonstrates the possibility of producing large quantities of engraftable skeletal myogenic cells from human PSCs.
多能干细胞（PSCs）的分化是一种有前途的方法，可以获得大量用于疾病建模和基于细胞的治疗的成骨肌祖细胞。然而，产生具有高再生潜力的成骨肌细胞仍然具有挑战性。我们最近报道了从鼠 PSC 衍生的畸胎瘤中产生的成骨肌祖细胞具有强大的再生能力。我们还发现源自人 PSCs 的畸胎瘤中含有成骨肌群体。在这里，我们表明这些人 PSC 衍生的成骨肌祖细胞具有出色的植入能力。细胞表面标志物 CD82、ERBB3 和 NGFR 的组合可有效纯化成骨肌祖细胞。这些细胞表达 PAX7 并能够分化为 MHC+多核肌管。我们进一步发现这些细胞在体外可扩增。移植后，扩增的细胞形成了新的肌营养不良蛋白纤维，几乎重建了 ¾ 的总肌肉体积，并重新填充了肌肉干细胞池。因此，我们的研究表明，从人 PSCs 中产生大量可植入的成骨肌细胞是可能的。
