Hsp90 alpha promotes the migration of iPSCs-derived keratinocyte to accelerate deep second-degree burn wound healing in mice
Hsp90 alpha promotes the migration of iPSCs-derived keratinocyte to accelerate deep second-degree burn wound healing in mice
复制标题
Hsp90 α 促进 iPSC 来源的角质形成细胞迁移，加速小鼠深二度烧伤创面愈合
DOI：
10.1016/j.bbrc.2019.09.120
复制
发表时间：
2019
影响因子：
3.1
通讯作者：
Yan Yuan
中科院分区：
文献类型：
--
作者：
Wu Ruijun;Du Dan;Bo Yunyao;Zhang Min;Zhang Lin;Yan Yuan
由于诱导多能干细胞(IPSCs)的优势，IPSCs来源的角质形成细胞在创伤修复方面具有巨大的临床和研究潜力。与其他细胞移植疗法类似，IPSCs来源的角质形成细胞移植到皮肤中的迁移能力对治疗效果至关重要。热休克蛋白90α对角质形成细胞的迁移有促进作用。因此，本研究的目的是在深二度烧伤皮肤模型中观察热休克蛋白90α对移植的IPSCs来源的角质形成细胞的影响。首先，用RA和BMP4诱导IPSCs分化为角质形成细胞。接下来，我们解释了热休克蛋白90α对体外培养的IPSCs来源的角质形成细胞的影响。我们发现热休克蛋白90α促进了IPSCs来源的角质形成细胞的迁移。此外，在热休克蛋白90α诱导的IPSCs来源的角质形成细胞迁移中，AKT的激活是必需的。将PBS、HSP90α、IPSCs来源的角质形成细胞、IPSCs来源的角质形成细胞+HSP90α应用于深二度烧伤创面。通过大体评价和苏木精-伊红染色评价创面愈合情况。我们的结果表明，IPSCs来源的角质形成细胞加Hsp90α处理的创面比其他组的创面愈合速度明显加快。此外，IPSCs来源的角质形成细胞+Hsp90α组再生表皮中CFSE标记的IPSCs来源角质形成细胞的数量增加。综上所述，这些发现表明，联合应用IPSCs来源的角质形成细胞和Hsp90α可能是一种有前途的伤口愈合治疗策略。
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 vitro. 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.