Identification of a Novel Hierarchy of Endothelial Progenitor Cells Utilizing Human Peripheral and Umbilical Cord Blood

Emerging evidence to support the use of endothelial progenitor cells (EPC) for angiogenic therapies or as biomarkers to assess cardiovascular disease risk and progression is compelling. However, there is no uniform definition of an EPC, which makes interpretation of these studies difficult. Though a hallmark of stem and progenitor cells is their ability to proliferate and give rise to functional progeny, EPC are primarily defined by expression of cell surface antigens. Here, utilizing adult peripheral and umbilical cord blood, we describe an approach that identifies a novel hierarchy of EPC based on their clonogenic and proliferative potential, analogous to the hematopoietic cell system. In fact, some EPC form replatable colonies when deposited at the single cell level. Using this approach, we also identify a previously unrecognized population of EPC in cord blood that can achieve at least 100 population doublings, replate into at least secondary and tertiary colonies, and retain high levels of telomerase activity. Thus, these studies describe a clonogenic method to define a hierarchy of EPC based on their proliferative potential, and identify a unique population of high proliferative potential-endothelial colony forming cells (HPP-ECFC) in human umbilical cord blood.