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Granulocyte colony-stimulating factor (G-CSF) depresses angiogenesis in vivo and in vitro: implications for sourcing cells for vascular regeneration therapy.

TitleGranulocyte colony-stimulating factor (G-CSF) depresses angiogenesis in vivo and in vitro: implications for sourcing cells for vascular regeneration therapy.
Publication TypeJournal Article
Year of Publication2010
AuthorsTura O, Crawford J, Barclay GR, Samuel K, Hadoke PWF, Roddie H, Davies J, Turner ML
JournalJ Thromb Haemost
Volume8
Issue7
Pagination1614-23
Date Published2010 Jul
ISSN1538-7836
KeywordsAnimals, Blood Vessels, Endothelial Cells, Granulocyte Colony-Stimulating Factor, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cells, Humans, Male, Mice, Mice, Inbred C57BL, Neovascularization, Physiologic, Paracrine Communication, Regeneration, Stem Cells, Umbilical Veins
Abstract

SUMMARY 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.

PATIENTS/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.

DOI10.1111/j.1538-7836.2010.03900.x
Alternate JournalJ. Thromb. Haemost.
PubMed ID20456757
PubMed Central IDPMC3404501
Grant ListPG/06/051 / / British Heart Foundation / United Kingdom
PG/06/051/20781 / / British Heart Foundation / United Kingdom