Circulating endothelial progenitors in vascular repair

Abstract

Endothelial progenitor cells (EPCs) display pro-angiogenic properties that confer to them a therapeutic potential for treating ischemic lesions. In culture, EPCs generate Endothelial Colony Forming Cells (ECFCs) that have endothelial features but still retain properties of stem/progenitor cells. EPCs can be obtained either from cord blood (CB) or adult blood (AB). For clinical perspectives, both CB-ECFCs and AB-ECFCs have advantages and inconveniences. On one hand, CB-ECFCs are allogenic, with potential immune rejection, but are more clonogenic, proliferative and angiogenic than AB-ECFCs. We have found that these cells display high inter-individual variation in terms of clonogenic profile. Low clonogenic CB-ECFCs had functional properties similar to those of AB-ECFCs. Conversely, a high initial clonogenicity was associated to an enhanced proliferation, angiogenic potential and to an increased expression of genes linked to stem cell-ness. Selecting CB-ECFCs according the initial clonogenicity represent a relevant marker of their potential efficacy on vascular repair. On the other hand, AB-ECFCs are autologous, and should be immunologically well tolerated, but these cells give rise to only few colonies, proliferate less and are less angiogenic than CB-ECFCs. In order to go further in CB-/AB- characterization, we have analyzed the mechanisms of AB-ECFC premature senescence, and shown that GDF15 had pivotal role in this context. Taken together, these new data constitute important steps toward clinical use of EPCs.