超声协同纳米微泡提高帕金森小鼠移植干细胞存活率的实验研究

项目名称： 超声协同纳米微泡提高帕金森小鼠移植干细胞存活率的实验研究

项目编号： No.81471678

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： 谢明星

作者单位： 华中科技大学

项目金额： 80万元

中文摘要： 干细胞移植对帕金森动物有肯定疗效，但临床应用效果不稳定，原因之一是移植细胞存活率低。超声协同微泡能增加缺血动物模型干细胞存活率。本课题组前期研究表明，低频超声协同纳米级微泡可开放超声辐照区血脑屏障，如能应用该技术使干细胞经静脉输注后通过血脑屏障并提高脑内存活率，将促进帕金森病干细胞疗法的临床应用。本课题旨在研究应用低频超声协同纳米级微泡开放中脑血脑屏障后使经静脉输注神经干细胞（NSCs）迁移入脑的可行性，观察不同技术参数对脑内移植细胞存留率的影响及其安全阈值，在此基础上，应用优化后技术介导经静脉输注干细胞治疗帕金森小鼠模型，并与纹状体立体定向注射移植方式对比，通过行为学检测、免疫组化、病理和电镜观察、PCR、高效液相色谱法等观察两种移植途径脑内NSCs存活、分化情况以及疗效，以评估经静脉途径移植干细胞治疗帕金森病的临床应用价值。

中文关键词： 超声靶向微泡破坏；神经干细胞；帕金森病

英文摘要： Stem cell transplantation was identified to be effective in the Parkinson animal models but the clinic therapeutic effect was not very stable. One of the reasons was the low survival rate of the transplantated cells. Ultrasound-targeted microbubble destruction could enhance the survival rate of stem cells in ischemic animal models. Our previous study suggested that nano-scale microbubble destruction induced by low-frequency ultrasound could open the localized blood-brain barrier in irradiation area. If this technique could be used to force the stem cells through the blood-brain barrier after intravenous infusion and improve the cell survival rate in the brain, it will promote the clinical application of neural stem cell therapy in the Parkinson's disease. The aims of this research are to evaluate the feasibility of the intravenous neural stem cells (NSCs) migrating into the brain through the opened midbrain blood-brain barrier by ultrasound-mediated nano-scale microbubble destruction, and to observe the effect of the technical parameters to the cell retention in the brain and their safety thresholds. Based on these, the optimized technique will be further used to force the intravenous neural stem cell to the brain to treat Parkinson's rat models. The survival and differentiation of the transplanted NSCs and the efficacy of the treatment will be assessed by the behavioral tests, immunohistochemical method, pathology and electron microscopic observation, PCR and high performance liquid chromatography to evaluate the clinical value of intravenous stem cells transplantation in the treatment of Parkinson's disease compared with the stereotactic injection transplantation in the striatum.

英文关键词： Ultrasound-targeted microbubble destruction;Neural stem cells;Parkinson's disease