MiR-21-5p-enriched exosomes from hiPSC-derived cardiomyocytes exhibit superior cardiac repair efficacy compared to hiPSC-derived exosomes in a murine MI model  

作　　者：Jing-Jun Jin Rong-Hua Liu Jin-Yan Chen Kun Wang Jun-Yong Han Dao-Shun Nie Yu-Qing Gong Bin Lin Guo-Xing Weng 

机构地区：[1]Fujian Key Laboratory of Medical Analysis,Fujian Academy of Medical Sciences,Fuzhou 350001,Fujian Province,China [2]Shengli Clinical Medical College,Fujian Medical University,Fuzhou 350001,Fujian Province,China

出　　处：《World Journal of Stem Cells》2025年第3期81-101,共21页世界干细胞杂志(英文)

基　　金：Supported by the Nonprofit Research Institutes Foundation of Fujian Province,China,No.2021R1012005 and No.2021R1012003.

摘　　要：BACKGROUND Heart disease remains a leading cause of mortality worldwide,with existing treatments often failing to effectively restore damaged myocardium.Humaninduced pluripotent stem cells(hiPSCs)and their derivatives offer promising therapeutic options;however,challenges such as low retention,engraftment issues,and tumorigenic risks hinder their clinical utility.Recent focus has shifted to exosomes(exos)-nanoscale vesicles that facilitate intercellular communication-as a safer and more versatile alternative.Understanding the specific mechanisms and comparative efficacy of exos from hiPSCs vs hiPSC-derived cardiomyocytes(hiPSC-CMs)is crucial for advancing cardiac repair therapies.AIM To evaluate and compare the therapeutic efficacy of exos secreted by hiPSCs and hiPSC-CMs in cardiac repair,and to elucidate the role of microRNA 21-5p(miR-21-5p)in the observed effects.METHODS We differentiated hiPSCs into CMs using small molecule methods and characterized the cells and their exos.RESULTS Our findings indicate that hiPSC-CMs and their exos enhanced cardiac function,reduced infarct size,and decreased myocardial fibrosis in a murine myocardial infarction model.Notably,hiPSC-CM exos outperformed hiPSC-CM cell therapy,showing improved ejection fraction and reduced apoptosis.We identified miR-21-5p,a microRNA in hiPSC-CM exos,as crucial for CM survival.Exos with miR-21-5p were absorbed by AC16 cells,suggesting a mechanism for their cytoprotective effects.CONCLUSION Overall,hiPSC-CM exos could serve as a potent therapeutic agent for myocardial repair,laying the groundwork for future research into exos as a treatment for ischemic heart disease.

关 键 词：Human-induced pluripotent stem cells Human-induced pluripotent stem cell-derived cardiomyocytes Myocardial infarction EXOSOMES MicroRNA 21-5p Apoptosis 

分 类 号：R73[医药卫生—肿瘤]