Effects of erythropoietin in skin wound healing are dose related.
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
Heiko
H
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Krueger
Christian
C
Schulz
Torsten
T
Menger
Michael D
MD
Schmitz
Frank
F
Vollmar
Brigitte
B
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008833:Microcirculation; D018919:Neovascularization, Physiologic / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000293:injuries*; D012879:Skin Physiological Phenomena; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
D004921:Erythropoietin