Efficient Muscle Regeneration by Human PSC-Derived CD82(+) ERBB3(+) NGFR(+) Skeletal Myogenic Progenitors

卷:12

Article

关键词: P75 NEUROTROPHIN RECEPTOR;    SATELLITE CELLS;    SELF-RENEWAL;    STEM-CELLS;    HUMAN ES;    IN-VIVO;    EXPANSION;    MOUSE;    MODEL;    TRANSPLANTATION;   

DOI  :  10.3390/cells12030362

来源: SCIE

【 摘 要 】

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 3/4 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.