Efficacy of erythropoietin pretreated mesenchymal stem cells in murine burn wound healing: possible in vivo transdifferentiation into keratinocytes.

Abstract

BACKGROUND\nStem cells have shown promising potential to treat burn wounds. Erythropoietin was capable of promoting in vitro transdifferentiation of mesenchymal stem cells (MSCs). The aim of the study was to investigate possible role of erythropoietin pretreated mesenchymal stem cells (EPOa/MSCs) in burn wounds healing and to evaluate its in vivo differentiation into keratinocytes.\n\n\nMATERIALS AND METHODS\nForty rats were utilized in this study divided into 4 groups (n=10 for each). Control group (I), Burn group (II), Burn + MSCs, group (III), Burn + EPOa/MSCs. 1x10⁶ Cells were injected locally for each 1 cm² of burn areas. Burn areas were followed morphologically. After 21days of the experiment, the rats were euthanized, skin specimens were assessed biochemically, histologically and immunohistochemically.\n\n\nRESULTS\nEPOa/MSCs had enhanced significantly (p<0.05) burn wound vimentin gene expression and level of IL-10 while decreased IL-1 and COX2 as compared to the burn group. Histologically, EPOa/MSCs had improved epithelialization despite stem cells differentiation into keratinocytes had been rarely detected by PKH26 red fluorescence. EPOa/MSCs had promoted angiogenesis as detected by significant increase in VEGF and PDGF immunoexpression as compared to burn group.\n\n\nCONCLUSIONS\nEPOa/MSCs might improve burn wound healing probably through anti-inflammatory, immunomodulatory and angiogenic action. However, in vivo trandifferentiation into keratinocytes had been rarely detected.