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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1801-1809.
Prepublished online as a Blood First Edition Paper on October 19, 2006; DOI 10.1182/blood-2006-08-043471.


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PLENARY PAPER

Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals

Mervin C. Yoder1,3, Laura E. Mead1,2, Daniel Prater1,2, Theresa R. Krier1,2, Karim N. Mroueh1,2, Fang Li1,2, Rachel Krasich1,2, Constance J. Temm1,2, Josef T. Prchal4, and David A. Ingram1,3

1 Department of Pediatrics, 2 Herman B. Wells Center for Pediatric Research, 3 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis; 4 Division of Hematology/Oncology, Center for Cell and Gene Therapy, and Hematology, University of Utah, Salt Lake City

The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies "endothelial cell colony-forming units" (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.


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