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Late outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow.

TitleLate outgrowth endothelial cells resemble mature endothelial cells and are not derived from bone marrow.
Publication TypeJournal Article
Year of Publication2013
AuthorsTura O, Skinner EM, Barclay GR, Samuel K, Gallagher RCJ, Brittan M, Hadoke PWF, Newby DE, Turner ML, Mills NL
JournalStem Cells
Date Published2013 Feb
KeywordsAntigens, CD, Biological Markers, Bone Marrow Cells, Cell Lineage, Cells, Cultured, Endothelial Cells, Fetal Blood, Gene Expression, Granulocyte Colony-Stimulating Factor, Humans, Immunophenotyping, Leukocytes, Mononuclear, Neovascularization, Physiologic, Skin, Tissue Culture Techniques

A decade of research has sought to identify circulating endothelial progenitor cells (EPC) in order to harness their potential for cardiovascular regeneration. Endothelial outgrowth cells (EOC) most closely fulfil the criteria for an EPC, but their origin remains obscure. Our aim was to identify the source and precursor of EOC and to assess their regenerative potential compared to mature endothelial cells. EOC are readily isolated from umbilical cord blood (6/6 donors) and peripheral blood mononuclear cells (4/6 donors) but not from bone marrow (0/6) or peripheral blood following mobilization with granulocyte-colony stimulating factor (0/6 donors). Enrichment and depletion of blood mononuclear cells demonstrated that EOC are confined to the CD34(+)CD133(-)CD146(+) cell fraction. EOC derived from blood mononuclear cells are indistinguishable from mature human umbilical vein endothelial cells (HUVEC) by morphology, surface antigen expression, immunohistochemistry, real-time polymerase chain reaction, proliferation, and functional assessments. In a subcutaneous sponge model of angiogenesis, both EOC and HUVEC contribute to de novo blood vessel formation giving rise to a similar number of vessels (7.0 ± 2.7 vs. 6.6 ± 3.7 vessels, respectively, n = 9). Bone marrow-derived outgrowth cells isolated under the same conditions expressed mesenchymal markers rather than endothelial cell markers and did not contribute to blood vessels in vivo. In this article, we confirm that EOC arise from CD34(+)CD133(-)CD146(+) mononuclear cells and are similar, if not identical, to mature endothelial cells. Our findings suggest that EOC do not arise from bone marrow and challenge the concept of a bone marrow-derived circulating precursor for endothelial cells.

Alternate JournalStem Cells
PubMed ID23165527
Grant ListFS/10/024/28266 / / British Heart Foundation / United Kingdom
/ / Medical Research Council / United Kingdom