胚胎干细胞来源的功能性类胰岛组织体外培养及其机制研究

Stem cell-derived β cells transplantation is a promising cell therapy for patients with diabetes. However, cannot generate functional, mature β-cells in sufficient quantities in vitro becomes a limitation following β cells transplantation. To overcome this problem, differentiation the stem cell into organoids in vitro raised a new strategy in the laboratory. In this study, we will establish an efficient approach for generating islet like organoids through mimicking the natural surroundings of islet in term of culture hESC on ultra-low attachment plates or biometic-metrigel .Then study the mechanism of three-dimensional (3D) culture on hESC differentiation. Finally, we will assesse the competence of glucose-contral with hESC–derived ILO in vivo. This researchwould provide an unprecedented cell source for drug discovery and cell transplantation therapy in diabetes.

在干细胞定向诱导分化为胰岛β细胞的研究中，难以获得高效分化并功能成熟的β细胞是限制其应用的主要瓶颈，细胞乃器官的一部分，在体外模拟完整器官微环境，系统的获得类器官样组织，使目的细胞在器官中协调发育成熟，将成为干细胞分化应用的一个重要方向。本项目以人胚胎干细胞（hESCs）为材料，利用生物凝胶和悬浮培养体系在体外模拟构建体内胰岛生长三维微环境，同时根据胰岛发育过程中各种信号通路优化不同的小分子组合，建立hESCs向类胰岛的体外分化模型，通过细胞形态学和功能试验观察hESCs来源类胰岛的功能成熟情况，在此基础上从三维结构微环境对干细胞分化影响的角度探讨ESCs定向分化的可能机制，最后，通过类胰岛组织的体内移植实验，对其做为糖尿病细胞治疗的可行性进行分析。本研究将为干细胞来源的类胰岛组织用于药物研发或糖尿病细胞治疗奠定基础。