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

Abstract

SPECIFIC AIMSThe optimal cell population to be transplanted for therapeutic revascularization of ischemic tissues remains undetermined. We have compared the therapeutic potential of two subsets of human cord blood CD34+ progenitors that express or do not express the VEGF-A receptor 2 (KDR). As major treatment end-points, we considered 1) the level of hemodynamic recovery from ischemia, 2) histological evidence of microvascular and skeletal myofiber regeneration, and 3) protection from ischemia-induced apoptosis and replacement fibrosis.PRINCIPAL FINDINGS1. CD34+KDR+ cell transplantation enhances the neovascularization response to ischemia and protects from apoptosisThe proangiogenic action of transplanted CD34+KDR+ cells was tested in immunodeficient mice submitted to operative unilateral limb ischemia. As shown in Fig. 1⤻ A, transplantation of 103 CD34+KDR+ cells increased capillary density of ischemic muscles by 114% (1408±96 vs. 659±28 cap/mm2 in contralateral normoperfused adductors, P<0.01). No furth...