Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.
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.
Yoder
Mervin C
MC
Department of Pediatrics, Indiana University School of Medicine, Indianapolis 46202, USA.
Mead
Laura E
LE
Prater
Daniel
D
Krier
Theresa R
TR
Mroueh
Karim N
KN
Li
Fang
F
Krasich
Rachel
R
Temm
Constance J
CJ
Prchal
Josef T
JT
Ingram
David A
DA
D000328:Adult; D000818:Animals; D000941:Antigens / Q000378:metabolism; D015415:Biomarkers; D002454:Cell Differentiation; D017690:Cell Transplantation; D002478:Cells, Cultured; D002999:Clone Cells / Q000166:cytology*; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006413:Hematopoietic System / Q000166:cytology*; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009154:Mutation / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*
D000941:Antigens; D015415:Biomarkers; D053614:Janus Kinase 2