Transplanted cord blood-derived endothelial precursor cells augment postnatal neovascularization

Endothelial precursor cells (EPCs) have been identified in adult peripheral blood. We examined whether EPCs could be isolated from umbilical cord bloo d, a rich source for hematopoietic progenitors, and whether in vivo transpl antation of EPCs could modulate postnatal neovascularization. Numerous cell clusters, spindle-shaped and attaching (AT) cells, and cord-like structure s developed from culture of cord blood mononuclear cells (MNCs). Fluorescen ce-trace experiments revealed that cell clusters, AT cells, and cord-like s tructures predominantly were derived from CD34-positive MNCs (MNCCD34+). AT cells and cell clusters could be generated more efficiently from cord bloo d MNCs than from adult peripheral blood MNCs. AT cells incorporated acetyla ted-LDL, released nitric oxide, and expressed KDR, VE-cadherin, CD31, and v on Willebrand factor but not CD45. Locally transplanted AT cells survived a nd participated in capillary networks in the ischemic tissues of immunodefi cient nude rats in vivo. AT cells thus had multiple endothelial phenotypes and were defined as a major population of EPCs. Furthermore, laser Doppler and immunohistochemical analyses revealed that EPC transplantation quantita tively augmented neovascularization and blood flow in the ischemic hindlimb . In conclusion, umbilical cord blood is a valuable source of EPCs, and tra nsplantation of cord blood-derived EPCs represents a promising strategy for modulating postnatal neovascularization.