CD34-/CD133+/VEGFR-2+ endothelial progenitor cell subpopulation with potent vasoregenerative capacities

Our goal was to identify functionally important subpopulations within the heterogenous group of endothelial progenitor cells (EPC). Fluorescence-activated cell sorter analysis of CD133(+) progenitor cells revealed the presence of CD34(+) and CD34(-) subpopulations. CD34(-)/133(+) progenitors differentiate into CD34(+)/133(+) EPC, adhere more potently than these in response to SDF-1, and rapidly home to sites of limb ischemia in human volunteers. In human coronary atherectomy samples, fewer CD34(-)/133(+) than CD34(+)/133(+) EPC are present in stable plaques, whereas cell numbers increase with a reversion of the ratio in unstable lesions. In CD34(-)/133(+) EPC-injected nude mice, more transplanted cells coexpressing endothelial markers home to carotid artery lesion endothelium than in CD34(+)/133(+)-injected mice. In the former, lesions were smaller and reendothelialization higher than in the latter. We identified a new CD34(-)/133(+) EPC subpopulation, which is apparently a precursor of "classical" CD34(+)/133(+) EPC, and functionally more potent than these with respect to homing and vascular repair.