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Published as doi: 10.1096/fj.08-109991.
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(The FASEB Journal. 2009;23:3049-3058.)
© 2009 FASEB

Effects of erythropoietin in skin wound healing are dose related

Heiko Sorg*, Christian Krueger*, Torsten Schulz*, Michael D. Menger{dagger}, Frank Schmitz{ddagger} and Brigitte Vollmar*,1

* Institute for Experimental Surgery, University of Rostock, Rostock, Germany; and

{dagger} Institute for Clinical and Experimental Surgery and

{ddagger} Institute of Anatomy, University of Saarland, Homburg-Saar, Germany

1 Correspondence: Institute for Experimental Surgery, University of Rostock, Schillingallee 69a, 18055 Rostock, Germany. E-mail: brigitte.vollmar{at}med.uni-rostock.de

The hematopoietic growth factor erythropoietin (EPO) attracts attention due to its all-tissue-protective pleiotropic properties. We studied the effect of EPO on dermal regeneration using intravital microscopy in a model of full dermal thickness wounds in the skin-fold chamber of hairless mice. Animals received repetitive low doses or high doses of EPO (RLD-EPO or RHD-EPO) or a single high dose of EPO (SHD-EPO). SHD-EPO accelerated wound epithelialization, reduced wound cellularity, and induced maturation of newly formed microvascular networks. In contrast, RHD-EPO impaired the healing process, as indicated by delayed epithelialization, high wound cellularity, and lack of maturation of microvascular networks. Also, RHD-EPO caused an excessive erythrocyte mass and rheological malfunction, further deteriorating vessel and tissue maturation. Moreover, RHD-EPO altered fibroblast and keratinocyte migration in vitro, while both cell types exposed to RLD-EPO, and, in particular, to SHD-EPO showed accelerated wound scratch closure. In summary, our data show that a single application of a high dose of EPO accelerates and improves skin wound healing.—Sorg, H., Krueger, C., Schulz, T., Menger, M. D., Schmitz, F., Vollmar, B. Effects of erythropoietin in skin wound healing are dose related.


Key Words: microcirculation • cell migration • apoptosis • angiogenesis • epithelialization • pericytes







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