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Defining endothelial progenitor cells
Author(s) -
Yoder Mervin C,
Ingram David A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a867-c
Subject(s) - vasculogenesis , progenitor cell , haematopoiesis , angiogenesis , monocyte , microbiology and biotechnology , endothelial stem cell , endothelial progenitor cell , biology , macrophage , immunology , endothelium , stem cell , in vitro , cancer research , biochemistry , endocrinology
New vessel formation occurs via vasculogenesis, angiogenesis, or arteriogenesis. Since 1997, post‐natal vasculogenesis has been purported to be an important mechanism for angiogenesis via marrow‐derived circulating endothelial progenitor cells (EPCs). Emerging evidence suggests that EPC are derived from monocytes. We have used a commercially available assay for circulating human EPC that enumerates “colony forming unit‐endothelial cell” (CFU‐EC) activity and we correlated CFU‐EC formation with markers for monocytes, macrophages, and endothelium and these results were compared to endothelial colony forming cells (ECFC) isolated from the same blood samples. CFU‐ECs display evidence of their monocyte/macrophage lineage by retaining expression of c‐fms and non‐specific esterase activity. CFU‐EC can be plucked and replated in hematopoietic CFC assays to give rise to colony forming unit‐macrophages, however, cells plucked from a CFU‐EC colony are not capable of proliferation at a single cell level. In contrast, ECFC display a hierarchy of proliferative potentials at the single cell level, fail to display monocyte/macrophage antigens, and do not form hematopoietic CFC. CFU‐EC lack robust in vitro capillary tube formation, however, CFU‐EC co‐localize with ECFC formed capillary tubes. A whole cell proteomics analysis indicates differences in expression of several hundred proteins between CFU‐EC and ECFC. Human ECFC, but not CFU‐EC, implanted subcutaneously in immunodeficient mice spontaneously form vessels that function to carry murine blood cells. Thus, CFU‐EC are macrophages. We propose a revised model for considering the cellular events involved in new vessel formation emphasizing the interacting role of macrophages and ECFC.