Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury

作者：Qiancheng Luo, Dongfeng Guo, Guorong Liu, Guo Chen, Hang Min, Mingming Jin · 发表于：Cellular Physiology and Biochemistry · 年份：2017 · DOI：10.1159/000485949 · 被引用次数：270 · 研究领域：Extracellular vesicles in disease、Mesenchymal stem cell research、Cardiac Fibrosis and Remodeling

BACKGROUND/AIMS: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). METHODS: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. RESULTS: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel® and Transwell® assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with ...