Yoder MC, Mead LE, Prater D, et al. Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals. Blood 2007;109:1801-9.
Endothelial progenitor cells (EPCs) are the focus of intense investigation because of a need to define the cells for their use as potential therapeutic tools in conditions such as cardiovascular damage and to understand their relationship to hematopoietic precursors. Although animal models indicate that new vessel formation following injection of endothelial progenitor cells is a promising therapeutic intervention, the findings are not recapitulated in humans, and the true endothelial potential of EPCs is under question. This paper re-addresses the isolation and definition of the population of cells that form endothelial cells (ECFCs; endothelial colony-forming cells) and compares them to CFU-EC (endothelial colony-forming units) that are defined by commercially available assays. Comparing two distinct cell culture strategies, the investigators established that ECFCs originate from adherent cells whereas CFU-ECs arise from a non-adherent population. Yoder et al. note that CFU-ECs express hematopoietic markers and, more specifically, have myeloid regenerating capacity but no ability to form blood vessels. CFU-ECs differentiate into phagocytic macrophages, whereas the EPCs proliferate and form vessels, but do not form hematopoietic cells. Finally, taking advantage of the newly described JAK-2 mutation, the investigators put forth an argument that because all CFU-ECs but only a small fraction of ECFC contain the mutation, the former are derived from a hematopoietic precursor and the two populations are not clonally related.
The connection between early hematopoietic precursors and the ability to form blood vessels or support blood cell development continues to be defined, and this paper moves us one step closer to understanding the divide between these processes. The investigators do a careful job of delineating differences between the two populations of cells and note that previous identification of the precursor cells was defined by cell surface markers that may have selected for a population of cells with hematopoietic potential. Their assay relies on growth and colony formation in cell culture on defined surfaces and demonstrates that, from a pooled population of mononuclear blood cells, there were cells capable of both replicating and forming blood vessels that did not have hematopoietic markers. In contrast, the CFU-ECs cells did not replicate and were not capable of forming blood vessels. In part, the identification of unique populations may be obscured by the selection markers used, and, as the authors point out, the vascular formation potential of the cells was not reviewed — this may be a necessary component of analysis. With clearer insight into the cells of interest, it may be time to revisit cell-based therapy and characterize the molecular connection between these two populations of cells.
