title: Granulocyte colony-stimulating factor (G-CSF) depresses angiogenesis in vivo and in vitro: implications for sourcing cells for vascular regeneration therapy.
abstract: BACKGROUND
  The most common source of hematopoietic progenitor cells (HPCs) for hematopoietic reconstitution comprises granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs). It has been proposed that endothelial progenitor cells (EPCs) share precursors with HPCs, and that EPC release may accompany HPC mobilization to the circulation following G-CSF administration.
  
  
  OBJECTIVE
  To investigate EPC activity following HPC mobilization, and the direct effects of exogenous G-CSF administration on human umbilical vein endothelial cells (HUVECs) and endothelial outgrowth cells (EOCs), using in vitro and in vivo correlates of angiogenesis.
  
  
  METHODS
  Heparinized venous blood samples were collected from healthy volunteers and from cord blood at parturition. G-CSF-mobilized samples were collected before administration, at apheresis harvest, and at follow-up. PBSCs were phenotyped by flow cytometry, and cultured in standard colony-forming unit (CFU)-EPC and EOC assays. The effect of exogenous G-CSF was investigated by addition of it to HUVECs and EOCs in standard tubule formation and aortic ring assays, and in an in vivo sponge implantation model.
  
  
  RESULTS
  Our data show that G-CSF mobilization of PBSCs produces a profound, reversible depression of circulating CFU-EPCs. Furthermore, G-CSF administration did not mobilize CD34+CD133- cells, which include precursors of EOCs. No EOCs were cultured from any mobilized PBSCs studied. Exogenous G-CSF inhibited CFU-EPC generation, HUVEC and EOC tubule formation, microvessel outgrowth, and implanted sponge vascularization in mice.
  
  
  CONCLUSIONS
  G-CSF administration depresses both endothelial cell angiogenesis and monocyte proangiogenic activity, and we suggest that any angiogenic benefit observed following implantation of cells mobilized by G-CSF may come only from a paracrine effect from HPCs.
authors.affiliation: SNBTS Cell Therapy Group, MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK. olga.tura@ed.ac.uk
authors.forename: O
authors.initials: O
authors.lastname: Tura
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: G R
authors.initials: GR
authors.lastname: Barclay
authors.forename: K
authors.initials: K
authors.lastname: Samuel
authors.forename: P W F
authors.initials: PW
authors.lastname: Hadoke
authors.forename: H
authors.initials: H
authors.lastname: Roddie
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: M L
authors.initials: ML
authors.lastname: Turner
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019899:Paracrine Communication; D012038:Regeneration / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
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