Cdc42在iPS源性的角质形成细胞修复皮肤创伤中的调控机制研究

项目名称： Cdc42在iPS源性的角质形成细胞修复皮肤创伤中的调控机制研究

项目编号： No.81501677

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 闫媛

作者单位： 南方医科大学

项目金额： 18万元

中文摘要： 皮肤大面积创伤的临床修复方法目前尚存在着多种缺陷， iPS细胞技术则为其提供了新的治疗途径。目前研究显示iPS细胞源性角质形成细胞的移植治疗能促进小鼠皮肤创伤的修复，但对影响创伤愈合的关键因素-角质形成细胞的功能调控目前尚无报道。本课题组前期研究揭示在角质形成细胞介导的皮肤创伤修复中小G蛋白-Cdc42起到了重要作用，由此，在iPS细胞源性角质形成细胞中Cdc42是否参与了对其功能的调控？是否可以通过调节Cdc42的活性以增强iPS细胞源性角质形成细胞修复皮肤创伤的效果？因此本研究聚焦于探明Cdc42对iPS源性角质形成细胞体外增殖、迁移和分化功能的调控作用，阐明其中Cdc42与 Wnt/β-catenin通路及 PAK信号分子可能的相互信号网络；并进一步体内实验探讨Cdc42对iPS源性角质形成细胞移植治疗皮肤创伤的影响。旨在通过本研究为iPS细胞技术最终能够运用于临床提供理论研究基础。

中文关键词： 诱导多潜能干细胞；细胞移植；；皮肤损伤；Cdc42；角质形成细胞

英文摘要： Skin massive burns often result in open wounds and the treatment of rapid surgical closure with appropriate materials are required . Although the surgical closures with autologous epidermal grafts are effective, they have several disadvantages including donor site morbidity, time constraint, and limited cell yield from primary explanted keratinocytes. Induced pluripotent stem cell (iPSC) could offer the better way to meet the challenge of temporary skin replacement due to their unlimited proliferative capacity, multipotency to differentiate into multiple lineages, importantly and ethical acceptability. Although keratinocytes with the ability to reconstitute epidermal structures can be induced from iPSCs following exposure to retinoic acid and BMP4, the mechanisms controlling their functions in skin wound healing is poorly understood. Clearly, the study to reveal these mechanisms to enhance the clinical application of iPS-derived keratinocytes are required. Recently, we found the skin wound healing delay of the keratinocyte-restricted knockout Cdc42 mice, suggesting a critical role for Cdc42 during keratinocyte mediated skin wound healing. Therefore, we will observe the effect of Cdc42 on the proliferation, migration and differentiation of iPS cells-derived keratinocytes, and explore whether the Wnt/β-catenin and PAK signal pathways is involved or not. We also study the function of Cdc42 in iPS cells-derived keratinocytes mediated skin wound healing in vivo. In our study, we hope to provide basis knowledge for application of iPS cell technology on skin wound repair in the future.

英文关键词： iPS cells;cell transplantation;skin wound;Cdc42;keratinocyte