This project follows the research approach of "energy metabolism analysis - microenvironment remodeling - cell remodeling - large animal validation". It intends to combine protein and metabolomics methods to deeply analyze the energy metabolism characteristics and molecular mechanisms of ischemic myocardium and transplanted MSCs. Based on this, potential intervention targets will be screened. On the one hand, the local microenvironment metabolism characteristics and energy supply of ischemic myocardium will be actively changed. On the other hand, ischemic adaptive MSCs will be remodeled through gene or pharmacological means in vitro. With the above optimal scheme, the preclinical large animal validation of MSCs cardiac transplantation will be carried out, and the optimization strategy of MSCs will be established to enhance energy utilization efficiency and survival after in vivo transplantation, thus promoting myocardial repair and regeneration.

请翻译:本项目按照“能量代谢解析—微环境改造—细胞改造—大动物验证”的研究思路,拟结合蛋白质和代谢组学方法深入解析缺血心肌及移植MSCs的能量代谢特点和分子机制,以此为基础,筛选潜在干预靶点,一方面通过主动改变缺血心肌局部微环境代谢特性及能量供应,另一方面在体外通过基因或药理学手段改造缺血自适应MSCs,结合上述优选方案,进行MSCs心脏移植的临床前大动物验证,建立MSCs优化策略,增强在体移植后能量利用效率和生存,促进心肌修复和再生。

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