Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice.
Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice.
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DOI：
10.1016/j.yexcr.2019.111627
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发表时间：
2019-12
影响因子：
3.7
通讯作者：
Yuan Yan;J. Jiang;Min Zhang;Yinghua Chen;Xueer Wang;Mianbo Huang;Lin Zhang
中科院分区：
文献类型：
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作者：
Yuan Yan;J. Jiang;Min Zhang;Yinghua Chen;Xueer Wang;Mianbo Huang;Lin Zhang
诱导多能干细胞（iPSC）由于其无限增殖能力、多能性（multiplepotential）成多个谱系以及重要的伦理可接受性而为严重皮肤伤口愈合的管理提供了新的方法。在这项研究中，我们的目的是诱导iPSC分化为角质形成细胞，并观察移植iPSC衍生的角质形成细胞对小鼠伤口愈合的治疗作用。在这里，小鼠iPSC已成功分化为角质形成细胞。接下来，将CSFE标记的iPSC衍生的角质形成细胞直接注射到全层皮肤伤口中。进行苏木精和伊红、Masson三色、EdU染色和免疫组织化学染色以评估iPSC衍生的角质形成细胞对伤口愈合的影响。我们的结果显示，将iPSC衍生的角质形成细胞移植到全层皮肤伤口部位加速了上皮再形成并减少了瘢痕形成。此外，我们发现诱导多能干细胞来源的角质形成细胞条件培养液可降低成纤维细胞α-SMA和COL 1的表达，并增加MMP 1的表达。进一步的机制研究表明，TNF-α诱导的NF-κB活化参与了iPSC源性角质形成细胞条件培养液对成纤维细胞的作用。总之，本研究表明，iPSC衍生的角质形成细胞通过增加上皮形成率和减少瘢痕形成来缩短愈合时间，这表明可能的皮肤伤口愈合的新治疗。
Induced pluripotent stem cells (iPSCs) provide new approaches for the management of severe skin wound healing due to their infinite proliferative capacity, pluripotency into multiple lineages, and important ethical acceptability. In this study, we aimed to differentiate iPSCs into keratinocytes and to observe the therapeutic effects of transplanted iPSCs-derived keratinocytes on wound healing in mice. Here, mouse iPSCs had been successfully differentiated into keratinocytes. Next, iPSCs-derived keratinocytes labeled by CSFE were injected directly into the full-thickness skin wound. Hematoxylin & Eosin, Masson's trichrome, EdU staining and immunohistochemical staining were performed to assess the effects of iPSCs-derived keratinocytes on wound healing. Our results showed that transplantation of iPSCs-derived keratinocytes into full-thickness skin wound site accelerated re-epithelialization and reduced scar formation. In addition, we found that conditioned medium of iPSCs-derived keratinocytes reduced the expression of α-SMA and COL1 and increased the expression of MMP1 in fibroblastsin vitro. Further mechanism studies show the TNF-α-induced activation of NF-κB is involved in the effect of conditioned medium of iPSCs-derived keratinocytes on fibroblasts. In conclusion, this study has shown that iPSCs-derived keratinocytes decrease the healing time by increasing the epithelization rate and reduce scarring, suggesting a possible new treatment for skin wound healing.