Striking differences of distinct endothelial progenitor cell subtypes in coronary collateral formation and ischemia-mediated neovascularization: implications for therapeutic angiogenesis

Endothelial progenitor cells (EPCs) are strongly implicated in angiogenesis. However, results from EPC clinical trials have been underwhelming and contradictory, possibly due to the use of unselected cell populations. Two distinct EPC subtypes (early EPCs and late-outgrowth endothelial cells, OECs) have been found to exhibit different angiogenic properties in vitro but have rarely been compared in vivo. To investigate, we compare EPC properties in patients with CAD and murine models. In patients with single-vessel CAD involving the left anterior descending artery (n=26, age=63±10, male=81%) a positive correlation was found between the extent of coronary collateralization (invasively assessed) and OEC numbers (r=0.405,p=0.045), migration (r=0.578,p=0.006) and tubulogenesis (r=0.65,p=0.005). Patients with adequate vs inadequate collateralization (CFI≥0.25 vs <0.25) had better OEC characteristics (p<0.02). No correlation was found with early EPCs. Consistent with this, xenotransplantation of human OECs enhan...