NCE Year 6
The financial support from the CIRM has enabled us to develop an effective protocol for deriving progenitor cells from humane embryonic stem cells. A manuscript describing these results have been published in PLoS One . The ESC-derived cells wee find to undergo myogenic differentiation both in vitro and in vivo. The differentiated cells were positive for Pax3, Myf5, design, and MyoG. We also demonstrated that the presence of WNT3A in culture significantly promoted the myogenic commitment of these hESC-derived progenitor cells. In vivo transplantation of these committed cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice reveals survival and engraftment of the donor cells. The cells contributed to the regeneration of damaged muscle fibers and the satellite cell compartment. In lieu of the limited cell source for treating skeletal muscle defects, the hESC-derived PDGFRA(+) cells exhibit significant in vitro expansion while maintaining their myogenic potential. The results described in this study provide a proof-of-principle that myogenic progenitor cells with in vivo engraftment potential can be derived from hESCs without genetic manipulation. A manuscript based on these results is published in Nature Scientific Reports. During the course of these studies we have also developed a biomaterials assisted cell delivery approach to improve the survival, continued differentiation, and contribution of the transplanted cells to muscle tissue repair. Our findings show that the biomimetic material-assisted delivery of hESC-derived myogenic progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID mice significantly promotes survival and engraftment of transplanted cells in a dose-dependent manner (>200 fold improvement). A manuscript describing the results have been published recently in ACS Biomaterials.