GENE EXPRESSION % THERAPEUTIC APPLICATION OF MUSCLE STEM CELLS

Children'S Hospital Boston, Boston MA

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Abstract

DESCRIPTION (provided by applicant): The broad objectives of this proposal are to characterize human muscle stem cells and evaluate their potential as gene vectors for the therapy of muscle disorders. The aims of these studies are to 1) Purify muscle stem cells from human skeletal muscle, using the vital DNA dye Hoechst 33342 (H0342) and the fluorescence-activated cell sorter (FACS); 2) Use gene chip and gene array technologies to characterize the repertoire of genes expressed by human muscle stem cells and compare this to expression patterns in more differentiated myoblasts; 3) Analyze and characterize expressed genes that are specific to muscle stem cells to define possible pathways of differentiation/commitment of skeletal muscle stem cells; 4) Use the information derived from gene array technology to optimize different media compositions that will promote the propagation of human muscle stem cells in vitro; 5) Test whether human muscle stem cells can differentiate into multiple cell types in vivo by introducing them into NOD /SCID mice and assessing their ability to reach host skeletal muscles from the circulation. These studies are essential to further our basic knowledge on the existence of muscle stem cells in humans. The identification of candidate genes that are uniquely expressed by human muscle stem cells will help in understanding how muscle stem cells differ from more committed myoblasts, and start to unravel why muscle stem cells (at least from previous mouse studies) can differentiate into bone marrow. Further, exploring methods to propagate muscle stem cells will be crucial to obtain large numbers of cells for characterization experiments as well as in vivo studies. These in vivo studies are aimed to test whether human muscle stem cells can be safely used as vehicles to systemically deliver genes to skeletal muscle. The hope is to be able to extend the practical use of muscle stem cells in the development of a therapy for human muscle disorders.