间充质干细胞在原发性胆汁性肝硬化中作用的探究

项目名称： 间充质干细胞在原发性胆汁性肝硬化中作用的探究

项目编号： No.81471614

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： 费允云

作者单位： 中国医学科学院北京协和医院

项目金额： 65万元

中文摘要： 原发性胆汁性肝硬化（PBC）是一种由于免疫系统对自身肝脏进行攻击而引起的慢性胆汁淤积性肝病，在我国发病率呈逐年上升趋势，其发病机制未明，治疗药物单一，最终导致纤维化及肝硬化。间充质干细胞（MSCs）是成体干细胞的一种，其对免疫失衡具有调节作用，近年来在多种免疫相关疾病中表现出良好的抑制或治疗作用。本研究旨在探讨MSCs在PBC这种自身免疫性肝病中所发挥的作用。本课题将在我们前期研究的基础上，利用国际公认的dnTGF-βRII转基因PBC模型鼠和PBC患者数据库的平台，建立MSCs培养体系，比较PBC组和对照组的MSCs各项生物指标的差异，体外探究MSCs对PBC疾病相关效应性细胞抑制功能及相关机制，体内探究MSCs对PBC疾病在细胞水平可能具有的免疫调节作用，并探索与MSCs功能相关的分子机制。试图将基础研究成果转化为临床应用，验证MSCs对PBC患者的治疗作用，寻找治疗PBC的新方法。

中文关键词： 原发性胆汁性肝硬化；间充质干细胞；自身免疫病

英文摘要： Primary biliary cirrhosis (PBC) is an autoimmune liver disease triggered by immune system,which attacks liver and causes chronic cholestasis.There is an upward trend in the incidence of the disease in our country, which lacks effective treatments,and the pathogenesis is unclear. Mesenchymal stem cells (MSCs) is a kind of adult stem cells and it has an obvious modulatory effect on immune imbalance. In a variety of immune related diseases in recent years, MSCs also showed good inhibitory or therapeutic effect. Therefore, in present study, we propose application of MSCs to PBC,a typical autoimmune liver disease, using the internationally recognized dnTGF-βRII transgenic PBC disease model mice and PBC patients database.We establish MSCs culture system,comparing various biological indicators of PBC models and patients with heathy controls.Furthermore, we explore the MSCs' probable role and the internal mechanism of cell and molecular biology, hoping that MSCs' application could provide certain theoretical support for clinical treatment of PBC. In vitro, we elucidate the inhibitory effects of MSCs on CD4+ and CD8+ T cell functions and related mechanisms in PBC; in vivo, we explore the immunomodulatory role of MSCs for PBC disease at cellular level, and investigate the molecular mechanism of MSCs. In addition,we try to transfer basic research to clinical applications, verifying the therapeutic effect of MSCs on PBC patients,looking for a novel intervention against PBC.

英文关键词： Primary biliary cirrhosis;Mesenchymal stem cells;Autoimmune and autoimmune disease