Muscular Dystrophy (MD) is an ultimately lethal disease associated with long-term disability and suffering. Cellular therapy for muscular dystrophy is based on the hypothesis that replacement of muscle cells expressing the missing or defective gene (e.g. dystrophin) with normal muscle cells will result in phenotypic correction of the disease. We hypothesize that cellular therapy will be facilitated by early gestational transplantation of a myogenic stem cell population, and that engraftment of stem cells with normal genotype will lead to progressive replacement of the dystrophic muscle compartment. We will test this hypothesis by identifying promising myogenic stem cell populations derived from fetal and adult sources and transplanting these cells into fetal mice at 14 days gestation, a developmental stage that recapitulates the normal ontogeny of axial muscle stem cell population. Donor and recipient mice will be utilized that optimize detection of satellite and muscle cell differentiation, and that mimic the severity of human MD. The goal of these experiments is to establish a new approach to cellular therapy for muscular dystrophy that takes maximal advantage of normal developmental events during formation of the effected muscle compartment. ? ? ?
