The ever-elusive endothelial progenitor cell: Identities, functions and clinical implications

The concept of an Endothelial Progenitor Cell (EPC) that participates in adult angiogenesis is less than a decade old, yet it has received a great deal of attention due to its potential for cell-based clinical therapies in many pathologies. However, controversy remains as to the identity of this bone marrow-derived cell type and its ability to give rise to new endothelium in the adult. Reports on the contribution of EPCs to new vessels in ischemic tissue or tumors vary widely, ranging from 80-90% to negligible. As researchers hone their ability to identify, isolate, and expand these cells by their markers and functionality, mounting evidence suggests that they might constitute multiple, but related cell types. At least two general phenotypes have emerged from studies of bone marrow-derived cells contributing to angiogenesis: one that incorporates into the endothelial wall directly contributing to vascular expansion and another that is able to home to neovessels, but it locates behind the endothelial wall. Nonetheless, experimental evidence indicates that this second cell type supports the viability of newly formed vessels and thus it is equally relevant to neovascular growth. As our understanding of neovascularization in pathologic states expands, a more clear definition of the multiple cellular components required for the process will shed light into new models of therapeutic intervention. The identification of a cell type that could be isolated, expanded and infused into a patient would be very useful for promoting angiogenesis in ischemia, myocardial infarct and other pathologies.