Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice

被引：12
|
作者：
Yan, Yuan [1 ,2 ]
Jiang, Jie [1 ]
Zhang, Min [1 ]
Chen, Yinghua [1 ]
Wang, Xueer [1 ]
Huang, Mianbo [1 ]
Zhang, Lin [1 ,2 ]
机构：
[1] Southern Med Univ, Sch Basic Med Sci, Dept Histol & Embryol, Guangzhou 510515, Guangdong, Peoples R China
[2] Guangdong Prov Key Lab Construct & Detect Tissue, Guangzhou 510515, Guangdong, Peoples R China
来源：
EXPERIMENTAL CELL RESEARCH | 2019年 / 385卷 / 01期
基金：
中国国家自然科学基金;
关键词：
iPSCs-derived keratinocytes; Epithelialization; Scar; Collagen; alpha-SMA; MMP1; TNF-alpha; NECROSIS-FACTOR-ALPHA; FACTOR-KAPPA-B; CULTURED EPITHELIAL AUTOGRAFTS; PLURIPOTENT STEM-CELLS; GROWTH-FACTOR-BETA; BURN WOUNDS; GENE-TRANSCRIPTION; LUNG FIBROBLASTS; INDUCTION; DIFFERENTIATION;
D O I：
10.1016/j.yexcr.2019.111627
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 alpha-SMA and COL1 and increased the expression of MMP1 in fibroblasts in vitro. Further mechanism studies show the TNF-alpha-induced activation of NF-kappa B 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.
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页数：10
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