OP9-DL1诱导的异基因前T细胞联合IL-7转染的间充质干细胞修复化疗损伤小鼠胸腺结构和功能研究

项目名称： OP9-DL1诱导的异基因前T细胞联合IL-7转染的间充质干细胞修复化疗损伤小鼠胸腺结构和功能研究

项目编号： No.81670110

项目类型： 面上项目

立项/批准年度： 2017

项目学科： 医药、卫生

项目作者： 胡锴勋

作者单位： 中国人民解放军军事科学院军事医学研究院

项目金额： 25万元

中文摘要： 胸腺是人体重要的中枢免疫器官，白血病放化疗会对胸腺造成严重损伤，导致免疫恢复时间延迟，严重感染，恶性肿瘤复发。如何修复放化疗后的胸腺结构，组织，及促进T细胞快速发育一直是血液、免疫专家的研究热点。胸腺组织结构破坏，释放修复、促归巢细胞因子减少，外周造血干、祖细胞数量缺乏是胸腺组织功能损伤的关键三要素。前期工作利用IL7基因转染MSC促进损伤胸腺微环境修复的研究获得较好结果，并观察到体外OP9-DL1诱导的前T细胞促进了骨髓源造血干细胞在化疗白血病小鼠胸腺的归巢及长期存活。但缺少体内持续促胸腺细胞发育的功能和作用机制研究。因此，本课题希望在既往的工作基础上，继续探讨OP9-DL1诱导的前T细胞联合骨髓源造血干、祖细胞对胸腺结构，功能及促进T细胞发育的作用及机制探讨。

中文关键词： 胸腺损伤；造血微环境；T细胞发育；造血干细胞；间充质干细胞

英文摘要： Thymus is an important central immune organ. The chemotherapy and radiotherapy on leukemia can cause serious damage to the thymus, which leads to the delay of immune recovery, serious infection, even then the recurrence of malignant tumor. How to repair the thymus structure, tissue, and promote the rapid development of T cells has been the focus of the study of the hematological and immunological experts. Three key elements of thymus function injury were the thymus structure damaging, repair, and promote homing cytokine releasing reduced and peripheral hematopoietic stem, progenitor cells lacking. Previous work using Mesenchymal stem cells (MSC) with IL-7 transfection to promote the recovery of the damaged thymus microenvironment. And observed early T cell induced by in vitro op9-dl1 promote bone marrow hematopoietic stem cells in the homing and long term engraftment of thymus of leukemia mice after chemotherapy, but the lack of research on improving the function and mechanism of thymocytes development. Therefore, this study aims to explore the effect and mechanism of OP9-DL1induced T cells combined with hematopoietic stem and progenitor cells improving recovery of thymus structure, function and promoting the development of T cells.

英文关键词： thymus injuried;hematopoietic microenvironment;T cell development;heatopoietic stem cells;mesenchymal stem cells