GLP-1旁分泌优化MSCs与胰岛细胞共移植治疗糖尿病及其监测的研究

项目名称： GLP-1旁分泌优化MSCs与胰岛细胞共移植治疗糖尿病及其监测的研究

项目编号： No.81471688

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张一帆

作者单位： 上海交通大学

项目金额： 70万元

中文摘要： 胰岛细胞移植是根治1型糖尿病的有效方法，但目前的治疗策略尚不能有效改善移植后胰岛β细胞的长期存活和功能。研究发现，胰岛细胞内潜在的胰高血糖素样肽-1（GLP-1）旁分泌可有效地保护胰岛β细胞，促进其再生修复、增殖和抗凋亡，同时刺激胰岛素的合成分泌；而间充质干细胞（MSCs）与胰岛细胞共移植具有促进血管新生和降低机体对胰岛细胞免疫排斥的作用。结合前期研究基础，我们拟利用杆状病毒介导MSCs表达并旁分泌GLP-1，通过一系列分子生物学方法检测其与胰岛细胞体外共培养和体内共移植时对胰岛细胞长期的存活和功能状态的协同改善作用。同时，利用18F标记的GLP-1类似物exendin-4进行胰岛β细胞GLP-1R的Micro PET/CT显像，以实时和定量地监测GLP-1旁分泌优化MSCs与胰岛细胞共移植治疗糖尿病,评估其对胰岛细胞移植后长期状态的改善作用，为胰岛细胞移植治疗糖尿病提供极具潜力的新策略。

中文关键词： 胰高血糖素样肽-1；旁分泌；间充质干细胞；糖尿病；分子显像

英文摘要： Islet cells transplantation is a effective way to radically cure type 1 diabetes, but present therapy strategies are not ideal for improving long-term survival and function of transplanted islet cells. It has been found that the potential glucagon-like peptide-1 (GLP-1) paracrine secretion in islet cells can effectively protect beta cells by improving their regeneration, proliferation and anti-apoptosis, as well as promoting insulin synthesis and secretion. On the other hand, mesenchymal stem cells (MSCs) and islet cells co-transplantation has the effect on promoting angiogenesis and reducing immune rejection to the islet cells. Combining with early research work, we propose to use baculovirus to mediate MSCs paracrining GLP-1, then co-culture and co-transplant these GLP-1 paracrining-MSCs with islet cells, to evaluate the synergistic effect of combining the GLP-1 paracrine with MSCs co-transplantation (co-culture) on improving long-term survival and function of transplanted islet cells by a series molecular biology method. At the same time, we will use 18F labeled exendin-4 (GLP-1 analogue) to perform GLP-1R Micro PET/CT imaging for real-timely and quantitatively monitoring islet transplantation therapy by combining GLP-1 paracrine with MSCs co-transplanting, and evaluating its improvement on islet cells long-term survival and function after transplantation, thus providing a novel and potential strategy for islet cells transplantation therapy.

英文关键词： Glucagon-like Peptide-1;Paracrine;Mesenchymal Stem Cells;Diabetes;Molecular Imaging