Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Int J Mol Sci. 2023 Feb 26;24(5):4577. doi: 10.3390/ijms24054577.
Induced pluripotent stem cell (iPSC) therapy brings great hope to the treatment of myocardial injuries, while extracellular vesicles may be one of the main mechanisms of its action. iPSC-derived small extracellular vesicles (iPSCs-sEVs) can carry genetic and proteinaceous substances and mediate the interaction between iPSCs and target cells. In recent years, more and more studies have focused on the therapeutic effect of iPSCs-sEVs in myocardial injury. IPSCs-sEVs may be a new cell-free-based treatment for myocardial injury, including myocardial infarction, myocardial ischemia-reperfusion injury, coronary heart disease, and heart failure. In the current research on myocardial injury, the extraction of sEVs from mesenchymal stem cells induced by iPSCs was widely used. Isolation methods of iPSCs-sEVs for the treatment of myocardial injury include ultracentrifugation, isodensity gradient centrifugation, and size exclusion chromatography. Tail vein injection and intraductal administration are the most widely used routes of iPSCs-sEV administration. The characteristics of sEVs derived from iPSCs which were induced from different species and organs, including fibroblasts and bone marrow, were further compared. In addition, the beneficial genes of iPSC can be regulated through CRISPR/Cas9 to change the composition of sEVs and improve the abundance and expression diversity of them. This review focused on the strategies and mechanisms of iPSCs-sEVs in the treatment of myocardial injury, which provides a reference for future research and the application of iPSCs-sEVs.
诱导多能干细胞（iPSC）疗法为心肌损伤的治疗带来了巨大的希望，而细胞外囊泡可能是其作用的主要机制之一。iPSC 衍生的小细胞外囊泡（iPSCs-sEVs）可以携带遗传物质和蛋白质物质，并介导 iPSC 与靶细胞之间的相互作用。近年来，越来越多的研究集中在 iPSCs-sEVs 在心肌损伤中的治疗效果上。iPSCs-sEVs 可能是一种新的无细胞基于治疗心肌损伤的方法，包括心肌梗死、心肌缺血再灌注损伤、冠心病和心力衰竭。在当前的心肌损伤研究中，广泛使用了从 iPSCs 诱导的间充质干细胞中提取的 sEVs。用于治疗心肌损伤的 iPSCs-sEV 分离方法包括超速离心、等密度梯度离心和大小排阻色谱法。尾静脉注射和胆管内给药是最广泛使用的 iPSCs-sEV 给药途径。进一步比较了来自不同物种和器官的 iPSCs 诱导的成纤维细胞和骨髓等来源的 sEVs 的特征。此外，可以通过 CRISPR/Cas9 调节 iPSC 的有益基因，改变 sEV 的组成，提高其丰度和表达多样性。本综述重点介绍了 iPSCs-sEVs 治疗心肌损伤的策略和机制，为未来的研究和 iPSCs-sEVs 的应用提供了参考。
