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

Abstract

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. Hsp90α had a positive effect on migration of keratinocytes. Therefore, the aim of this study was to investigate the effects of Hsp90α 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 Hsp90α on iPSCs-derived keratinocyte in\xa0vitro. We found that hsp90α promoted cell migration of iPSCs-derived keratinocyte. Furthermore, activation of AKT was required for Hsp90α-induced iPSCs-derived keratinocyte migration. Then PBS, Hsp90α, iPSCs-derived keratinocyte, and iPSCs-derived keratinocyte plus Hsp90α 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 Hsp90α 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 Hsp90α group. In summary, these findings represent that combined administration of iPSCs-derived keratinocyte and Hsp90α may be a promising therapeutic strategy for wound healing.