| 초록 |
The ability of human embryonic stem cells (hESCs) to differentiate into skeletal muscle cells and contribute to tissue regeneration has shown great promise to treat debilitating skeletal muscle diseases. However, efficient differentiation of hESCs into skeletal muscle cells and their in vivo survival and function within host tissues upon transplantation remains a daunting task. Here, we report that hESC-derived mesoderm progenitor cells expressing PDGFRA, platelet-derived growth factor receptor-α, can undergo myogenic differentiation without any genetic manipulation. This was evidenced by expression of late myogenic markers, including DES, MYOG, MYH1, and sarcomeric myosin (MF20). Furthermore, to improve the in vivo functions of these transplanted cells, we developed a biomimetic polymer-based cell delivery vehicle consisting of hyaluronic acid backbone functionalized with acryloyl-6-aminoacproic acid moieties (HA-A6ACA) that can mimic the structural and functional properties of native proteoglycans. Our findings reveal that the biomaterial-assisted delivery of hESC-derived myogenic progenitors into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promoted survival and engraftment efficiency of the transplanted cells. The donor cells were found to contribute to the regeneration of damaged muscle fibers as well as to the satellite cell compartment. The results described in this study provide a proof-of-principle that hESC-derived myogenic progenitors have in vivo engraftment potential and employing biomimetic materials as a delivery vehicle could considerably promote in vivo survival and function of the transplanted cells. Such a cell delivery vehicle that is cost-effective and easy-to-synthesize offers an ideal tool to promote the outcomes of cell-based therapies. |
