Journal
BLOOD
Volume 109, Issue 5, Pages 1801-1809Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2006-08-043471
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Funding
- NCI NIH HHS [P30 CA82709, 1P01CA108671-01A2, P01 CA108671, P30 CA082709] Funding Source: Medline
- NHLBI NIH HHS [P50 HL085036, 1P01 HL085036] Funding Source: Medline
- NINDS NIH HHS [P50 NS052606] Funding Source: Medline
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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 colonyforming 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 CFUECs 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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