Erythropoietin Stimulates Wound Healing and Angiogenesis in Mice

Abstract

Erythropoietin exerts hematopoietic effects by stimulating proliferation of early erythroid precursors. Nonhematopoietic effects of erythropoietin have also been shown. It may act as a new angiogenic factor in wound healing. This study aimed to investigate the effect of systemic administration of recombinant human erythropoietin on wound healing in mice. Dorsal incisional wounds were performed in mice, which were then divided into two groups; a group treated for 7 days with recombinant human erythropoietin, and a control group. Sacrificing animals on day 7, the wound tissues were collected for analysis of wound breaking strength, malondialdehyde, a marker of lipid peroxidation, hydroxyproline, an index of reparative collagen deposition, reduced glutathione levels, and for histological evaluation. The immunohistochemical determination of vascular endothelial growth factor (VEGF) which is believed to be the most prevalent angiogenic factor throughout the skin repair process, was also studied. The treatment significantly increased wound breaking strength by decreasing malondialdehyde and increasing hydroxyproline levels on day 7 after wounding. No statistically meaningful change was observed in reduced glutathione content. VEGF was immunostained significantly more on wound tissue of treated animals compared to the control group. Recombinant human erythropoietin treatment may be effective in wound healing due to inhibition of lipid peroxidation, deposition of collagen, and VEGF expression in wound area.

Nonerythropoietic Tissue Protective Compounds Are Highly Effective Facilitators of Wound Healing

“…Further, tissue-specific stem cells are recruited by EPO to take up residence within the region of injury and differentiate into mature, functional cells (32). Finally, EPO also improves collagen deposition and modulates the number of fibroblasts within a wound site (13).…”

“…Among the pleiotropic effects of EPO reported, a number of investigators have reported significant activity of EPO in promoting the healing of ischemic raised cutaneous skin flaps (10)(11)(12)(13)(14), ischemiareperfusion in random musculocutaneous flaps (15), incisional wounds (10,13), and in colonic anastomoses (16,17). Additionally, skin thermal burns also have been reported to respond in a beneficial way to EPO (18).…”

Erythropoietin reduces lipopolysaccharide-induced cell Damage and midkine secretion in U937 human histiocytic lymphoma cells

“…Many studies have investigated the cytoprotective role of EPO and have led to its use in the treatment of a number of different disease models such as stroke, surgery and diabetes. [4][5][6] However, the potential role of EPO in the regulation of inflammatory cytokines, in particular by macrophages, has yet to be elucidated.…”

Erythropoietin ameliorates the reduced migration of human fibroblasts during in vitro hypoxia

“…EPO did not affect the VEGF release of HDMEC, but again NHDF were more susceptible to EPO, resulting in an efficient dampening of the VEGF release under hypoxia. Although several authors have described the enhanced expression of VEGF during EPO-mediated healing [8,36], the reduction of the VEGF level detected could also be a useful trigger of NHDF migration. A reduction could especially be important in the case of exorbitantly high VEGF concentrations appearing in the chronic wound as result of intense hypoxia, as it was simulated in the current model.…”