title: Erythropoietin ameliorates the reduced migration of human fibroblasts during in vitro hypoxia.
abstract: Erythropoietin promotes the formation of granulation tissue when administered to soft tissue wounds and it was shown to be most effective under tissue hypoxia. However, the action of erythropoietin on the cellular level is not well understood. In order to get a better insight into these processes, an in vitro wound healing assay was applied. Two main players of soft tissue healing-fibroblasts and microvascular endothelial cells-were used as mono- and co-cultures, subsequently inflicting in vitro wounds. Cell migration, proliferation, the differentiation of fibroblasts to myofibroblasts, and the release of vascular endothelial cell growth factor A and angiogenin were quantified in response to hypoxia and erythropoietin (5 IU/ml). Erythropoietin supplementation did neither affect proliferation nor migration of endothelial cells and fibroblasts under normoxia. Under hypoxia, the reduced fibroblast migration was ameliorated by erythropoietin. This effect coincided with an attenuated release of vascular endothelial growth factor A, whereas angiogenin release was unaffected by erythropoietin. The in vitro model applied in this study may represent an adequate approximation to certain aspects of the in vivo status of soft tissue regeneration and the results might serve to interpret the in vivo efficiency of erythropoietin at the cellular level: Erythropoietin has different impacts on the cells in normoxia and hypoxia. Its positive influence on fibroblast migration during hypoxia seems to support the strategies of applying erythropoietin in those chronic wounds, which exhibit fibroblastic dysfunction although good vascularisation is present.
authors.affiliation: Laboratory for Molecular and Cell Biology, Department of Trauma, Hand, and Reconstructive Surgery, Saarland University, Kirrberger Strasse, Bldng. No. 57, 66421 Homburg, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Breit
authors.forename: Monika
authors.initials: M
authors.lastname: Bubel
authors.forename: Tim
authors.initials: T
authors.lastname: Pohlemann
authors.forename: Martin
authors.initials: M
authors.lastname: Oberringer
mesh_terms: D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004921:Erythropoietin / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D058628:Myofibroblasts / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
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