经颅超声靶向微泡破裂技术促进静脉骨髓间充质干细胞移植靶向治疗小鼠缺血性脑卒中的研究

项目名称： 经颅超声靶向微泡破裂技术促进静脉骨髓间充质干细胞移植靶向治疗小鼠缺血性脑卒中的研究

项目编号： No.81501603

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王韩兵

作者单位： 哈尔滨医科大学

项目金额： 18万元

中文摘要： 缺血性脑卒中具有很高致死率和致残率。由于其现有治疗方法上的缺乏，目前正在进行大量相关研究，这其中即包括干细胞疗法。前期研究证实静脉移植骨髓间充质干细胞（BMSC）能够治疗小鼠脑缺血，但血脑屏障（BBB）的存在，限制了BMSC从外周血靶向缺血脑组织迁移的数量。经颅超声靶向微泡破裂（UTMD）能够促进BBB短暂、可逆性开放，但其能否促进BMSC向脑内迁移国内外尚无报道。前期研究中，我们首次通过经颅UTMD提高静脉注射VEGF基因质粒在缺血脑内的表达，并证实UTMD可逆、靶向开放BBB是促进VEGF基因在脑内表达的关键，因此我们推测经颅UTMD 能够促进静脉移植的BMSC向缺血脑内迁移，并发挥更佳的治疗效果。为证实此假说我们将复制小鼠脑缺血再灌注损伤模型，采用多种生物学技术观察经颅UTMD处理后静脉移植的BMSC向脑内迁移及其发挥的生物学作用。为微创、靶向干细胞移植治疗缺血性脑卒中提供新策略。

中文关键词： 干细胞移植；骨髓间充质干细胞；超声靶向微泡破裂；靶向治疗；缺血性脑卒中

英文摘要： Ischemic stroke has a very high mortality rate and disability rate. Due to the lack of the existing treatment methods, a large number of researches are under investigation, which include stem cell therapy. Although previous research confirmed that intravenous transplantation of bone marrow mesenchymal stem cells (BMSC) can be used for the treatment of cerebral ischemia in mice, but the blood brain barrier (BBB) exist, limiting the number of BMSC migration from peripheral blood of/into targeted ischemic brain tissue. Transcranial ultrasound targeted microbubble destruction (UTMD) can promote BBB transiently and reversiblly opening,but so far there is no domestic or foreign study reporting whether it could promote the migration of BMSC into the brain through BBB. In previous study, we for the first time used transcranial UTMD to enhance the expression of intravenously injected plasmid of VEGF gene in ischemic brain, and confirmed that UTMD reversibly and targetedly opening BBB is the key to promote the expression of VEGF gene in the brain. Therefore, we speculate that transcranial UTMD can also enhance the migration of intravenously grafted BMSC to the ischemic brain, and exert better therapeutic efficacy. In order to confirm this hypothesis, we will prepare the cerebral ischemia reperfusion injury model in mice, observe the effects of transcranial UTMD treatment on the migration of intravenously transplanted BMSC into the brain, and investigate their following biological effects on the ischemic brain by using immunofluorescence staining, molecular biology technology and so on. This minimally invasive, targeted stem cell transplantation method might provide a new therapeutic strategy for ischemic stroke.

英文关键词： stem cell transplant;bone marrow mesenchymal stem cell;ultrasound-targeted microbubble destruction;targeted therapy;ischemic stroke