Effects of Erythropoietin in Skin Regeneration and Repair

Lately erythropoietin (EPO), a hematopoietic substance, has been used increasingly to support, regenerate or repair tissue and organ functions. As the prevalence of chronic wounds is considerably increasing in an aging population, there is the need for supportive therapies in wound care management. The use of this pleiotropic glycoprotein hormone could therefore present widespread non-hematopoietic tissueprotective effects, which have also been evaluated in physiologic and pathologic skin wound healing. EPO interacts with different pathways relevant in wound healing, i.e., decrease of inflammation and apoptosis, enhancement of cell migration, as well as proliferation and maturation of microvessels. Despite ample experimental data referring to the tissue-protective effects of EPO, severe side effects occurred in clinical studies. Accordingly, the use of EPO beyond the treatment of chronic anemia and significant blood loss has again been questioned, also in skin wound healing. The challenge for the future with regard to skin regeneration and repair will therefore be (I) to improve the efficiency of alternative routes of EPO application, (II) to improve and engineer several well-tolerated EPO-like molecules, which induce all EPO-effects but erythropoiesis (III) to process and evaluate solid acting antibodies which are able to reliably provide evidence of EPO receptor on the respective tissues or cells and (IV) finally to promote randomized double blind controlled clinical studies which are able to describe potential safety concerns of EPO and so determine about its use in daily clinical routine. This book chapter therefore aims at describing the current knowledge on the use of EPO in different problems of skin wound healing in detail, critically discusses the potential underlying mechanisms and highlights the problems in its clinical use.

Keywords: Apoptosis, burn, dosing, epithelialization, EPO, microcirculation, skin, SMAD, TGF-β, vessel maturation.