项目名称: 过表达IDO大鼠骨髓间充质干细胞分泌Exosome在心脏移植存活中的作用及机制
项目编号: No.81460073
项目类型: 地区科学基金项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 贺继刚
作者单位: 云南省第一人民医院
项目金额: 47万元
中文摘要: 骨髓间充质干细胞(BMSCs)可通过旁分泌调节免疫反应。分泌囊泡(Exsome)具有调节免疫反应功能。吲哚胺2,3双加氧酶(IDO)通过降解局部组织中的色氨酸,发挥免疫调节作用。但过表达IDO的BMSCs及其分泌的Exosome与免疫调节的关系却鲜有研究。本实验室前期已经证明BMSCs过表达IDO可以加强免疫调节。进一步通过Transwell小室证明旁分泌具有重要作用。据此认为过表达IDO的BMSCs分泌的Exosome,可以加强同种异体心脏移植存活时间。本实验拟通过慢病毒转染BMSCs过表达IDO,提取分泌的Exosome采用RT-PC、液相芯片从细胞、因子水平及建立大鼠异位心脏移植模型从组织、动物层面验证免疫调节效果并采用表达谱芯片探讨Exosome免疫调节机制。本研究从Exosome这个新视点为揭示调节异体移植免疫排斥反应奠定基础,并为预防其发生提供新的思路。
中文关键词: 骨髓间充质干细胞;吲哚胺2;3双加氧酶;分泌囊泡;心脏移植
英文摘要: Secretory vesicles (Exsome) regulate the function of the immune response. Bone mesenchymal stem cells (BMSCs) can modulate the immune response. Indoleamine 2,3-dioxygenase (IDO) by degrading tryptophan local organizations play a role in immune regulation. However, overexpression IDO of BMSCs and Exosome secretion is rarely studied. The preliminary laboratory have demonstrated overexpression IDO of BMSCs can enhance immune regulation. Transwell chamber by further prove an important paracrine effects. Accordingly proposed a hypothesis that overexpression IDO BMSCs secreted Exosome, can enhance cardiac allograft survival time. To test this hypothesis BMSCs transfected by lentiviral overexpression IDO, Exosome secretion extracted using RT-PC, liquid chip from the cells, cytokine levels and the establishment of heterotopic heart transplantation in rats from the organization, animal level verification immunomodulatory effects and the use of microarrays to explore Exosome immunomodulatory mechanism. This study Exosome regulate this new viewpoint to reveal allograft immune rejection foundation and to prevent its occurrence to provide new ideas.
英文关键词: BMSCs;IDO;Exosome;Heart Transplant