低强度脉冲超声激励iPS诱导的神经嵴干细胞移植治疗脊髓损伤的实验研究

项目名称： 低强度脉冲超声激励iPS诱导的神经嵴干细胞移植治疗脊髓损伤的实验研究

项目编号： No.81472070

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： 宁广智

作者单位： 天津医科大学

项目金额： 72万元

中文摘要： 脊髓损伤（SCI）发病率高、致残率高，细胞移植治疗是目前的研究热点。而移植的种子细胞在SCI局部抑制性微环境难以存活并分化，因此获得高活性的种子细胞是急需解决的问题。课题组前期实验发现，低强度脉冲超声（LIPUS）能显著增强细胞的活性及增殖分化能力，而其最佳的干预方法及潜在的分子机制和信号通路并不清楚。本课题将以实验研究为基础，通过人工智能方法建模深入探索LIPUS干预的最佳方法以提高被移植细胞活力，进一步阐述其潜在的分子机制；同时从硬件和软件两方面进一步优化超声实验装置，使其能更适用于细胞实验。神经嵴干细胞（NCSCs）较其他多能干细胞具有更强的向神经细胞分化能力，因此本课题拟应用诱导多能干细胞（iPSCs）分化成的NCSCs，在LIPUS干预后将高活性iPSCs-NCSCs移植治疗SCI，观察其治疗效果和细胞增殖分化情况，为实现脊髓损伤的有效修复和早期康复提供新的思路。

中文关键词： 低强度脉冲超声；神经嵴干细胞；脊髓损伤；细胞移植；功能恢复

英文摘要： The rate of morbidity and disability of spinal cord injury (SCI) is high and thus currently the treatment of SCI concentrates on cell transplantation therapy. However, it is difficult for the transplanted seed cells to survive and differentiate in the inhibitory micro-environment after SCI, therefore how to obtain seed cellswith high viability is a big issue. The previous work shows that the low-intensity pulsed ultrasound（LIPUS）can significantly enhance the viability, proliferation and differentiation of cells, however,the best intervention methods and molecular mechanism, as well as signal pathways, are still not clear and to be investigated. The project is to explore the best LIPUS intervention on the basis of experimental research and modeled by artificial intelligence to improve the viability of seed cells and discover the molecular mechanisms. Meantime the experimental system is to be optimized in terms of both hardware and software in order to be more suitable for project experiments with cells. Neural crest stem cells (NCSCs) are better than other pluripotent stem cells in terms of differentiating to neurocytes. Therefore it is purposed to employ neural crest stem cells differentiated from induced pluripotent stem cells (iPSCs), with higher viability due to intervention by LIPUS,to be transplanted for treating SCI. The observation of the effect of iPSCs-NCSCs, intervened by LIPUS in the treatment of spinal cord injury, provides new ideas to achieve effective and early rehabilitation after spinal cord injury.

英文关键词： low-intensity pulsed ultrasound;neural crest stem cell;spinal cord injury;cell transplantation;functional recovery