title: Angiogenic murine endothelial progenitor cells are derived from a myeloid bone marrow fraction and can be identified by endothelial NO synthase expression.
abstract: OBJECTIVE
  Endothelial progenitor cells (EPCs) contribute to postnatal neovascularization and are therefore of great interest for autologous cell therapies to treat ischemic vascular disease. However, the origin and functional properties of these EPCs are still in debate.
  
  
  RESULTS
  Here, ex vivo expanded murine EPCs were characterized in terms of phenotype, lineage potential, differentiation from bone marrow (BM) precursors, and their functional properties using endothelial NO synthase (eNOS)-green fluorescent protein transgenic mice. Despite high phenotypic overlap with macrophages and dendritic cells, EPCs displayed unique eNOS expression, endothelial lineage potential in colony assays, and angiogenic characteristics, but also immunologic properties such as interleukin-12p70 production and low levels of T-cell stimulation. The majority of EPCs developed from an immature, CD31(+)Ly6C+ myeloid progenitor fraction in the BM. Addition of myeloid growth factors such as macrophage-colony-stimulating factor (M-CSF) and granulocyte/macrophage (GM)-CSF stimulated the expansion of spleen-derived EPCs but not BM-derived EPCs.
  
  
  CONCLUSIONS
  The close relationship between EPCs and other myeloid lineages may add to the complexity of using them in cell therapy. Our mouse model could be a highly useful tool to characterize EPCs functionally and phenotypically, to explore the origin and optimize the isolation of EPC fractions for therapeutic neovascularization.
authors.affiliation: Department of Immunology, Erasmus Medical Center, Dr Molewaterplein 50, 3015GE Rotterdam, Netherlands.
authors.forename: C J M
authors.initials: CJ
authors.lastname: Loomans
authors.forename: H
authors.initials: H
authors.lastname: Wan
authors.forename: R
authors.initials: R
authors.lastname: de Crom
authors.forename: R
authors.initials: R
authors.lastname: van Haperen
authors.forename: H C
authors.initials: HC
authors.lastname: de Boer
authors.forename: P J M
authors.initials: PJ
authors.lastname: Leenen
authors.forename: H A
authors.initials: HA
authors.lastname: Drexhage
authors.forename: T J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: A J
authors.initials: AJ
authors.lastname: van Zonneveld
authors.forename: F J T
authors.initials: FJ
authors.lastname: Staal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology / Q000502:physiology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D015415:Biomarkers; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052250:Nitric Oxide Synthase Type III