Our progress over the past year has significantly advanced the aims of this work: 1) Determine the cellular phenotypes of human muscle stem cells as they differentiate into myoblasts, and 2) Determine the ability of human muscle stem cells at different stages of development to engraft, proliferate and differentiate into muscle in a mouse model of muscular dystrophy, and determine their functional and myo-mechanical effects on dystrophic muscle. We now have a working system to derive early progenitor muscle cells from human embryonic stem cells. The differentiation protocol has been developed sufficiently such that skeletal muscle cells can be generated from human ES cells. We have identified points along the differentiation process at which muscle cells that are less mature and possibly more stem-like are prevalent. The data suggests that based on the genes the cells express at early stages, isolation and transplantation of cells at that stage but not further along will be most beneficial for transplantation and clinical application. This brings us a step closer to obtaining useful muscle cells that can be transplanted to treat muscle disorders. The current plan is to test these cells in muscle injury preclinical models to evaluate their capacity to regenerate injured muscle.