Role of Muscle Stem Cell Migration in Skeletal Muscle Growth and Regeneration

Primary supervisor: Professor Claire Stewart
Second supervisor: Dr Adam Sharples

Migration of skeletal muscle stem and progenitor cells is a pre-requisite for successful skeletal muscle development, post-natal growth and regeneration. It has implications not only for hypertrophic adaptation with age or chronic catabolic disease but also for the ultimate success or failure of myoblast transfer therapy, a proposed strategy for restoring normal dystrophin expression in dystrophic muscles. Despite the therapeutic potential of enhancing myoblast homing and ultimately cell fusion, the precise mechanisms facilitating these processes are not well understood. Never the less, reported research implicates the beneficial role of local or systemic growth factors (insulin-like and hepatic growth factors), matrix degrading enzymes and key signalling pathways (PI3- and MAP-kinases) on improved chemotaxis or migration of muscle cells. In order to ultimately improve the migration of myogenic cells in vivo, a better understanding of the intra- and extra-cellular regulators of myogenic cell migration is required. A combination of different strategies may be required, such as manipulation of soluble factors (proteomic analyses of secreted factors, qRT-PCR), genetic modifications of the donor cells (stable transfection and siRNA technology), or modulation of intracellular signalling pathways (cell culture, inhibitor studies (e.g. PTEN inhibition), siRNA, SDS PAGE, Western blotting, live cell imaging, FLOW cytometry) in order to optimise migration, homing and cell:cell fusion. Developing tools to enhance the migration of endogenous muscle progenitor cells could have important implications not only for the repair of muscle damage (e.g. in elite sport), but also in proposed therapies for muscle wasting disorders and would contribute to a better understanding of the process of skeletal muscle myogenesis and regeneration throughout the lifespan.