Hsp90α promotes the migration of iPSCs-derived keratinocyte to accelerate deep second-degree burn wound healing in mice

Because of the advantages of induced pluripotent stem cells (iPSCs), iPSCs-derived keratinocyte hold great clinical and research potential in wound repair. Similar to other cell transplantation therapies, the migration ability of iPSCs-derived keratinocyte transplanted into skin is critical to the therapeutic effect. Hsp90 alpha had a positive effect on migration of keratinocytes. Therefore, the aim of this study was to investigate the effects of Hsp90 alpha on transplanted iPSCs-derived keratinocyte in a skin model of deep second degree burns. First, keratinocytes were differentiated from iPSCs by treating with RA and BMP4. Next, we explained the effect Hsp90 alpha on iPSCs-derived keratinocyte in vitro. We found that hsp90 alpha promoted cell migration of iPSCs-derived keratinocyte. Furthermore, activation of AKT was required for Hsp90 alpha-induced iPSCs-derived keratinocyte migration. Then PBS, Hsp90 alpha, iPSCs-derived keratinocyte, and iPSCs-derived keratinocyte plus Hsp90 alpha were applied to the wound bed of deep second degree burns. Wound healing was assessed by gross evaluation and hematoxylin and eosin staining. Our results shown that wound treated with iPSCs-derived keratinocyte plus Hsp90 alpha significantly accelerates the rate of wound healing closure than other groups. In addition, the number of CFSE-labeled iPSCs-derived keratinocyte in regenerated epidermis was increased in iPSCs-derived keratinocyte plus Hsp90 alpha group. In summary, these findings represent that combined administration of iPSCs-derived keratinocyte and Hsp90 alpha may be a promising therapeutic strategy for wound healing. (C) 2019 Elsevier Inc. All rights reserved.