Exosomes derived from human umbilical cord mesenchymal stem cells can reverse ventricular remodeling and improve long-term cardiac function after acute myocardial infarction

作者：Renjie Wang, Lulu Liu, Fusheng Han, Qian Ma, Hua He · 发表于：Biochemical and Biophysical Research Communications · 年份：2025 · DOI：10.1016/j.bbrc.2025.151920 · 被引用次数：11 · 研究领域：Cardiac Fibrosis and Remodeling、Extracellular vesicles in disease、Tissue Engineering and Regenerative Medicine

BACKGROUND: Acute myocardial infarction (AMI) is the most common ischemic heart disease with high morbidity and high mortality. Although the treatment of AMI is constantly developing, ischemia-reperfusion (I/R) injury remains a complex problem. In recent years, human umbilical cord-derived mesenchymal stem cell-derived exosomes (hUC-MSC-EXO) have been shown to alleviate related damages. However, the long-term effects, safety, and mechanism of action have not yet been fully explored. METHODS: We constructed human umbilical cord-derived mesenchymal stem cell-derived engineered exosomes. We compared the short-term and long-term protective abilities of engineered exosomes on myocardium during I/R in cardiomyocytes and rat models, and determined their long-term safety. At the same time, key pathways and genes were predicted through exosome sequencing. RESULTS: hUC-MSC-EXO significantly reduced apoptosis, oxidative stress, and inflammation in both in vitro and in vivo models. In I/R rats, IMTP-EXO demonstrated superior cardioprotective effects, reducing myocardial fibrosis and improving left ventricular function compared to controls. Long-term studies showed enhanced ejection fraction (EF) and fractional shortening (FS) and reduced left ventricular end-diastolic dimensions (LVEDD). Fluorescence imaging revealed higher exosome accumulation in ischemic hearts. Genes related to cardiovascular diseases were obtained through cross-comparison of multiple databases. GO analysis revealed t...