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

Abstract

BACKGROUND: Stem 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. MATERIALS AND METHODS: Forty rats were utilised in this study divided into four groups (n = 10 for each). Control group (I), burn group (II), burn + MSCs, group (III), burn + EPOa/MSCs. 1 × 10⁶ cells were injected locally for each 1 cm² of burn areas. Burn areas were followed-up morphologically. After 21 days of the experiment, the rats were euthanised, skin specimens were assessed biochemically, histologically and immunohistochemically. RESULTS: EPOa/MSCs enhanced significantly (p < 0.05) burn wound vimentin gene expression and level of interleukin (IL)-10 while decreased IL-1 and COX2 as compared to the burn group. Histologically, EPOa/MSCs improved epithelialisation despite stem cells' differentiation into keratinocytes was rarely detected by PKH26 red fluorescence. EPOa/MSCs promoted angiogenesis as detected by significant increase in VEGF and PDGF immunoexpression as compared to burn group. CONCLUSIONS: EPOa/MSCs may improve burn wound healing, probably through anti-inflammatory, immunomodulatory and angiogenic action. However, in vivo transdifferentiation into keratinocytes was rarely detected.