Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood.
Emerging evidence to support the use of endothelial progenitor cells (EPCs) 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. Although hallmarks of stem and progenitor cells are their ability to proliferate and to give rise to functional progeny, EPCs are primarily defined by the expression of cell-surface antigens. Here, using adult peripheral and umbilical cord blood, we describe an approach that identifies a novel hierarchy of EPCs based on their clonogenic and proliferative potential, analogous to the hematopoietic cell system. In fact, some EPCs form replatable colonies when deposited at the single-cell level. Using this approach, we also identify a previously unrecognized population of EPCs 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 EPCs based on their proliferative potential, and they identify a unique population of high proliferative potential-endothelial colony-forming cells (HPP-ECFCs) in human umbilical cord blood.
Ingram
David A
DA
Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis 46202, USA. dingram@iupui.edu
Mead
Laura E
LE
Tanaka
Hiromi
H
Meade
Virginia
V
Fenoglio
Amy
A
Mortell
Kelly
K
Pollok
Karen
K
Ferkowicz
Michael J
MJ
Gilley
David
D
Yoder
Mervin C
MC
D001773:Blood Cells / Q000166:cytology*; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002999:Clone Cells; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D013234:Stem Cells / Q000145:classification / Q000166:cytology*; D019098:Telomerase / Q000378:metabolism
D019098:Telomerase