人子宫内膜上皮细胞来源iPS细胞定向分化用于子宫内膜再生的效应和机制研究

由机械或者感染等原因引起的子宫内膜基底层损伤，将导致子宫内膜纤维化、斑痕化、宫腔粘连及不孕，治疗困难。利用组织工程技术修复受损子宫内膜是一种非常具有前景的新手段，然而种子细胞来源困难，因此本课题将人子宫内膜上皮细胞来源诱导多能干细胞（iPS）细胞定向分化用于子宫内膜再生的效应和机制研究。利用iPS技术将自体子宫内膜上皮细胞重编程后再定向诱导分化成为人子宫内膜上皮前体/干细胞作为种子细胞，研究子宫内膜上皮干细胞的分化条件和机制，并用丝素蛋白微球作为组织工程支架包被血管内皮生长因子(VEGF)作为载体，用于体内研究修复子宫内膜损伤的效应。本项目发现将建立子宫内膜上皮细胞发育过程各个不同阶段模型，揭示子宫内膜分化各阶段的基因表达调控机制，获得基于自体来源种子细胞组织工程技术修复受损子宫内膜新方法。

Damage caused by mechanical force or infection to the basalis layer would disturb the self-repair of the endometrium, and subsequently cause fibrosis, scar formation, menstrual disorder, uterine adherence and infertility, which could hardly be cured. Tissue engineering is a promising new medical treatment.on the repair of damaged endometrium, however there is a lack of seed cells. Thus, this project aims at directed differentiation of induced pluripotent stem cells (iPS) into human endometrial epithelial progenitor stem cells and their application in the repair of mice model of endometrial injury. By using iPS technology, autologous somatic cells could be reprogrammed and subsequently re-differentiated into endometrial progenitor cells. Combining the endometrial progenitor cells as seed cells with silk fibroin microspheres as tissue engineering scaffolds so as to coat vascular endothelial growth factor (VEGF) and guide the growth and differentiation of seed cells, tissue engineering treatment on the repair of endometrial damage would be investigated. By conducting this project, developmental model of endometrial epithelia would be setup, and systematic investigation of the molecular regulatory network during the development of the endometrial epithelia could be viable, autologous cell based tissue engineering treatment on the repair of endometrial damage could also be developed.