Stem Cell Therapy for Myopathy

University Of Chicago, Chicago IL

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): The Muscular Dystrophies are a collection of disorders characterized by progressive muscle wasting. Duchenne Muscular Dystrophy and a subset of the Limb Girdle Muscular Dystrophies are caused by mutations in dystrophin and sarcoglycan, respectively. Disruption of the dystrophin glycoprotein complex results in sarcolemmal fragility, leading to muscle degeneration that eventually exceeds the regenerative capacity of muscle. There is currently no cure for muscular dystrophies. Stem cell transplantation is a promising therapeutic strategy for functional correction of dystrophic muscle. The therapeutic use of stem cell transplantation for muscular dystrophy has the advantage adding cells to the regenerative cell pool of muscle that contain normal copies of the defective genes. Ongoing challenges in optimizing a stem cell-based approach include identifying cells with potent myogenic activity, maintaining long-term survival of transplanted cells, and avoiding immune responses. The goal of this research is to identify stem cells from adult skeletal muscle that have the greatest potential to regenerate dystrophic muscle. For these studies, I will use a murine model of Limb Girdle Muscular Dystrophy, since these mice display a dystrophic phenotype without reverant fibers. Successful transplantation is documented in this model through restoration of the sarcoglycan complex. I will build on preliminary data showing that uncultured, mononuclear cells from muscle of adult mice have markedly improved regenerative potential over conventionally cultured myoblasts. I propose to test the long term survival and functional consequences of stem cell transplantation. I will assess the importance of the immune system using genetically modified or irradiated recipients. Lastly, I will use a sequential, double transplant system to select for improved markers with which to identify stem cells. The identification of improved markers of stem cells will allow for the rapid isolation and selection of uncultured stem cells for muscle regeneration. [unreadable] [unreadable] [unreadable]