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Blood, 1 November 2004, Vol. 104, No. 9, pp. 2752-2760.
Prepublished online as a Blood First Edition Paper on June 29, 2004; DOI 10.1182/blood-2004-04-1396.
Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood
David A. Ingram,
Laura E. Mead,
Hiromi Tanaka,
Virginia Meade,
Amy Fenoglio,
Kelly Mortell,
Karen Pollok,
Michael J. Ferkowicz,
David Gilley, and
Mervin C. Yoder
From the Department of Pediatrics, Herman B. Wells Center for Pediatric Research, the Department of Biochemistry and Molecular Biology, and the Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis.
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. (Blood. 2004;104:2752-2760)

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