Transplantation of low dose CD34+KDR+ cells promotes vascular and muscular regeneration in ischemic limbs

Abstract

Hematopoietic progenitor cell transplantation can contribute to revascularization of ischemic tissues. Yet, the optimal cell population to be transplanted has yet to be determined. We have compared the therapeutic potential of two subsets of human cord blood CD34+ progenitors, either expressing the VEGF-A receptor 2 (KDR) or not. In serum-free starvation culture, CD34+KDR+ cells reportedly showed greater resistance to apoptosis and ability to release VEGF-A, as compared with CD34+KDR- cells. When injected into the hind muscles in immunodeficient SCIDbg mice subjected to unilateral ischemia, a low number (10(3)) of CD34+KDR+ cells improved limb salvage and hemodynamic recovery better than a larger dosage (10(4)) of CD34+KDR- cells. The neovascularization induced by KDR+ cells was significantly superior to that promoted by KDR- cells. Similarly, endothelial cell apoptosis and interstitial fibrosis were significantly attenuated by KDR+ cells, which differentiated into mature human endothelial cells and also apparently skeletal muscle cells. This study demonstrates that a low number of CD34+KDR+ cells favors reparative neovascularization and possibly myogenesis in limb ischemia, suggesting the potential use of this cell population in regenerative medicine.