Effects of Erythropoietin in Skin Regeneration and Repair
Pp. 160-179 (20)
Heiko Sorg, Reto Wettstein, Peter M. Vogt and Yves Harder
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.
Apoptosis, burn, dosing, epithelialization, EPO, microcirculation,
skin, SMAD, TGF-β, vessel maturation.
Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.