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

Mervin C. Yoder, Laura E. Mead, Daniel Prater, Theresa R. Krier, Karim N. Mroueh, Fang Li, Rachel Krasich, Constance J. Temm, Josef T. Prchal, David A. Ingram

Research output: Contribution to journalArticle

1141 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1801-1809
Number of pages9
JournalBlood
Volume109
Issue number5
DOIs
StatePublished - Mar 1 2007

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Yoder, M. C., Mead, L. E., Prater, D., Krier, T. R., Mroueh, K. N., Li, F., Krasich, R., Temm, C. J., Prchal, J. T., & Ingram, D. A. (2007). Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood, 109(5), 1801-1809. https://doi.org/10.1182/blood-2006-08-043471