中文摘要
诱导多功能干细胞(induced pluripotent stem cell, iPSC)移植可改善心肌梗死后心功能,但心肌梗死后局部缺血缺氧微环境不利于干细胞的存活和分化。我们研究发现补气活血中药可优化移植微环境,促进干细胞的存活和分化,然而中药调控干细胞存活和分化的作用机制尚不清楚。本课题拟在补气活血中药促进iPSC移植治疗心肌梗死的基础上,通过特异信号通路荧光素酶报告基因、启动子荧光素酶报告基因和启动子控制表达的荧光报告iPSC细胞系筛选促进 iPSC存活和诱导iPSC向心肌细胞分化的有效成分,研究中药有效成分预处理iPSC移植治疗心肌梗死的作用,并通过基因过表达和基因沉默技术探讨PI3K/Akt和Wnt-11/JNK信号通路在中药调控iPSC存活和分化中的作用机制,不仅为解决干细胞移植面临的问题提供策略和手段,也为临床应用中药调控干细胞移植治疗心肌梗死提供理论依据和实验基础。
英文摘要
Transplantation of induced pluripotent stem cell (iPSC) could produce positive improvement on cardiac function after myocardial infarction (MI). However, the survival and differentiation of stem cells after transplantation was limited by the hypoxia-ischemia microenvironment. Our previous study found that Chinese medicine for replenishing qi and activating blood could optimize the microenvironment and improve the survival and differentiation of stem cells. However, the mechanisms on survival and differentiation of stem cell regulated by Chinese medicine are not very clear. This project intends to, on the basis of Chinese medicine promoting the effect of iPSC transplantation in the treatment of MI, select active ingredient enhancing the survival of iPSC and inducing the differentiation of iPSC into cardiomyocytes through specific signal luciferase reporter gene, cardiac cell-specific promoter TNNT2-luciferase reporter gene and TNNT2-GFP iPSC line, to investigate the effect of transplantation of iPSC pretreated with active ingredient from Chinese medicine, and to explore the mechanisms of PI3K/Akt and Wnt-11/JNK signaling pathway in Chinese medicine regulating survival and differentiation of iPSC through lentiviral gene overexpression and RNA interference technologies. This study could not only provide strategy and means to solve the problem of stem cell transplantation faces, but also provide theoretical basis and practical basis for the clinical application of stem cell transplantation regulated by Chinese medicine in the treatment of myocardial infarction.
