This study will examine the hypothesis that the function of diseased muscle in pediatric dystrophies may be improved by implantation of dissociated skeletal myoblasts. The proposal is predicated on the observation that myoblast implantation is feasible in skeletal muscle, allowing introduction of foreign genes and, in some models, improvement in function. Preliminary data in these investigations document the feasibility of implanting genetically labelled L6 myoblasts into skeletal muscle using both intra-arterial and intramuscular injections. Moreover, pilot preliminary data suggests the same cells may be implanted into ischemic rat heart muscle. This project intends to extend these observations with three specific aims: (1) study the feasibility of using intravascular delivery of cells rather than direct intramuscular injection, using both myocardial and skeletal muscle as host tissues; (2) determine whether a novel method of immunomasking of donor cells may be used to avoid rejection of donor myoblasts; and (3) ascertain whether these myoblasts may be implanted into and function within sites of myocardial injury where they fuse to form myotubes. The long-term goal is to further understand myoblast implantation, its immunobiology and the effects of milieu upon myoblast protein expression. Finally, this study will evaluate the feasibility of such intravascular cellular myoblast implantation as a therapy to augment skeletal and myocardial function in human muscle and heart diseases. The first phase of the PSA award will be devoted to obtaining (a) a better understanding of the scientific problems inherent in each of the specific aims and learning the laboratory techniques appropriate to each section. The second phase will be devoted to intense research and completion of the aforementioned aims.
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