Adult muscle stem cells possess remarkable regeneration properties and hold great promise in treating degenerative diseases such as muscular dystrophies, healing traumatic injuries and slowing age-related muscle loss. However, when these cells are isolated from the host and propagated in culture, they quickly lose their regenerative potency. As a result, they do not efficiently engraft or give rise to new muscle tissues following transplantation procedures. Our laboratory has developed a method to expand human muscle stem cells in culture conditions that retain their regenerative potency. In the past year, we have performed transplantation studies to confirm that these muscle stem cells expanded under controlled laboratory conditions maintain features of stem cells and high potency in tissue repair. Mice transplanted with these human muscle stem cells develop hybrid muscle fibers with both murine and human cellular components. These mice are useful models to provide more accurate assessment of the efficacy of gene therapy strategies using viral vectors in pre-clinical studies. We have also performed a systemic analysis to understand the functional regulation of these cells. Findings from these studies will give us cues on how to optimize therapeutic strategies involving human muscle stem cells.