Endothelial progenitor cells: quo vadis?

Abstract

The term endothelial progenitor cell (EPC) was coined to refer to circulating cells that displayed the ability to display cell surface antigens similar to endothelial cells in vitro, to circulate and lodge in areas of ischemia or vascular injury, and to facilitate the repair of damaged blood vessels or augment development of new vessels as needed by a tissue. More than 10 years after the first report, the term EPC is used to refer to a host of circulating cells that display some or all of the qualities indicated above, however, essentially all of the cells are now known to be members of the hematopoietic lineage. The exception is a rare viable circulating endothelial cell with clonal proliferative potential that displays the ability to spontaneously form inosculating human blood vessels upon implantation into immunodeficient murine host tissues. This paper will review the current lineage relationships among all the cells called EPC and will propose that the term EPC be retired and that each of the circulating cell subsets be referred to according to the terms already existent for each subset. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

Fig. 1

Role of various putative EPC in endothelial denudation injury. Following endothelial cell denudation injury, loss, or turnover, endothelial cells with proliferative potential (ECFC) divide and migrate to repair the injured area. This follows a series of events where platelets and proangiogenic hematopoietic cells are first recruited to the site of injury to facilitate repair.

Fig. 2

Putative EPC roles in angiogenesis. Resident endothelial cells with proliferative potential are likely to initiate sprouting, elongation, and inosculation leading to the formation of a new vessel in the presence of a stimulus such as a tumor. The circulating proangiogenic hematopoietic cells may play roles in disruption of the endothelial barrier properties, matrix degradation, promotion of endothelial cell sprouting, and endothelial capillary remodeling.

Fig. 3

Circulating ECFC display postnatal vasculogenic activity. Following traumatic injury to a tissue vasculature, hemostasis is initiated to prevent extensive hemorrhage. Rare circulating ECFC may become trapped within the clot and initiate vasculogenesis as a first step toward recanalization of the thrombus with or without subsequent vessel remodeling.