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1 Department of Medicine, New York Medical College, valhalla, ny, USA
2 Department of Orthopaedic Surgery, New York Medical College, valhalla, ny, USA
* To whom correspondence should be addressed. E-mail: michael_goligorsky{at}nymc.edu.
We have previously demonstrated that endothelial cells are severely damaged during renal ischemia/reperfusion and that transplantation of adult human endothelial cells into athymic nude rats subjected to renal ischemia resulted in a dramatic protection of the kidney against injury and dysfunction. Morphologic studies demonstrated the engraftment of transplanted cells into renal microvasculature. The goal of the present study was to determine the potential efficacy of in vitro expanded skeletal muscle-derived stem cells (MDSC) differentiated along the endothelial lineage in ameliorating acute renal injury. MDSC obtained from the Tie-2/green fluorescent protein (GFP) mice were used as donors of differentiated and non-differentiated stem cells. FVB mice, used as recipients, were subjected to renal ischemia and transplanted with the above MDSC. The differentiation of MDSC along the endothelial lineage was monitored by the appearance of Tie-2 promotor-driven expression of GFP. These MECA, eNOS, Flk-1, Flt-1, and CD31-positive cells engrafted into renal microvasculature and significantly protected short-term renal function after ischemia. Transplantation of non-differentiated MDSC characterized by the expression of Sca-1 (low levels of CD34, Flk-1, and cKit, and negative for GFP, eNOS and CD31) did not improve short-term renal dysfunction. In conclusion, the data a) provide a rich source of MDSC, b) delineate protocols for their in vitro expansion and differentiation along the endothelial lineage and c) demonstrate their efficacy in preserving renal function immediately after ischemic insult.
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