Endothelial progenitor cells: from bench to bedside

Strong evidence suggests that bone marrow-derived cells play a role in physiological and pathological blood vessel growth in the adult, both by augmenting angiogenesis through the secretion of angiogenic growth factors and by providing a rich source of progenitor cells that can differentiate into mature vascular endothelial cells. This is a true paradigm shift, since adult neovascularization processes were thought to be limited to angiogenesis. The cells that are critical to postnatal blood vessel growth - endothelial progenitor cells - may be analogous to the embryonic angioblast, in that they can circulate, proliferate and participate in the development of vascular networks by differentiating in situ, probably via the formation of cell clusters into mature endothelial cells. Therefore, initial reports have seen analogs to the process of vasculogenesis in the embryo, where the de novo synthesis of vessels occurs through the formation of blood island-like clusters, which subsequently connect and eventually form systemic vasculature. Recent work implicates precursors of endothelial cells in such processes as myocardial ischemia and infarction, limb ischemia, wound healing, atherosclerosis, endogenous endothelial repair and tumor vascularization. These new insights into the vascular biology of endothelial regeneration and repair led to the development of new cell therapeutic strategies to enhance adult neovascularization and re-endothelialization in ischemic cardiovascular diseases.