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New Advanced Technologies in Stem Cell Therapy
Final rept. 1 Sep 2009-31 Aug 2014
PITTSBURGH UNIV PA
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We have isolated and characterized a population of skeletal muscle-derived stem cells MDSCs that display a greatly improved skeletal and cardiac muscle transplantation capacity when compared to skeletal muscle myoblasts. The MDSCs ability to withstand oxidative and inflammatory stresses appears to be the single most important factor for their improved transplantation capacity. Although the true origin of MDSCs remains unclear, their high degree of similarity with blood vessel-derived stem cells suggests their potential origin could be from the vascular wall. We have recently isolated two distinct populations of cells from the vasculature of human skeletal muscle known collectively as human skeletal muscle-derived cells hMDCs. The two populations are myo-endothelial cells and pericytes and both can repair skeletal and cardiac muscles in a more effective manner than myoblasts, as is observed with murine MDSCs. In the current proposal we intend to evaluate and compare the regeneration capacity of these two hMDC populations after their implantation into the skeletal muscle of immunodeficientdystrophic SCIDmdx mice. We will then investigate the influence that sex has on the regeneration and repair capacity of the hMDCs endowed with the greatest regeneration capacity either myo-entothelial cells or pericytes. Finally we will investigate the influence that age plays on the regeneration capacity of the cells. Study Design We will investigate the effects of cell survival, proliferation, resistance to stress, and neoangiogenesis on the regeneration capacity of the hMDCs implanted into the skeletal muscle of SCIDmdx mice Since we have observed that female murine MDSCs display an improved transplantation capacity in skeletal muscle when compared to male MDSCs, we will determine the influence that sex has on the hMDCs.
APPROVED FOR PUBLIC RELEASE