急性心肌梗死中大量心肌细胞死亡，同种异体iPSCs来源的工程化心肌补片给紧急直接补充心肌细胞提供了潜在方向，但存在免疫排斥反应。本项目预实验以m6A甲基化修饰为切入点，针对同种异体iPSCs，利用CRISPR-Cas9技术在敲除人白细胞抗原I/II的基础上，进一步敲除m6A甲基转移酶Zc3h13，构建HCZ-iPSCs，初步发现HCZ-iPSCs来源的细胞具有极低的免疫原性；同时证明Fstl1多肽具有心肌保护性，并利用多巴胺，聚吡咯及Fstl1多肽初步合成支架材料PPFP。本项目拟进一步将HCZ-iPSCs来源的种子细胞接种于PPFP中，希望构建具有免疫豁免效应的新型心肌补片；同时对种子细胞的免疫原性，PPFP及心肌补片的理化性能，Zc3h13调控免疫原性的机制，以及心肌补片对心肌组织的再生修复作用进行研究。本项目的完成，将为解决心肌补片的免疫排斥反应提供新的方向。

A large number of cardiomyocytes died after acute myocardial infarction, and the engineered cardiac patch from allogeneic iPSCs provides a potential direction for the immediate supplement of cardiomyocytes, but there is immune rejection. In the pre experiment of this project, we focus on the methylation modification of m6A, for the allogeneic iPSCs, CRISPR-Cas9 technology was used to knock out the human leukocyte antigen I/II, and further knock out the m6A methyltransferase Zc3h13 to construct HCZ-iPSCs. It was found that HCZ-iPSCs derived cells had very low immunogenicity. Meanwhile, Fstl1 polypeptide had myocardial protection, and utilized dopamine, polypyrrole and Fstl1 polypeptide to construct the PPFP, a scaffold material. This project plans to further seed HCZ-iPSCs derived cells into PPFP, hoping to build a novel cardiac patch with immune exemption effect, at the same time, the immunogenicity of HCZ-iPSCs derived cells, the physical and chemical properties of PPFP and cardiac patch, the mechanism of Zc3h13 regulating immunogenicity, and the regeneration and repair of cardiac patch for cardiac tissue will be detected. The completion of this project will provide a new direction to solve the immune rejection of cardiac patch.