Exosomes derived from mir-214-3p overexpressing mesenchymal stem cells promote myocardial repair

Biomaterials Research

Research Article

Qingjie Wang¹  Yuan Ji¹  Ling Sun¹  Jianguang Jiang¹  Jian Zhang²  Haoran Wang³  Wenwu Zhu⁴  Xiu Hong⁴  Wei Du⁴  Rui Duan⁴  Bing Han⁴ 

[1] Department of Cardiology, the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China;Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Fudan University, 200000, Shanghai, China;Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, 210023, Nanjing, China;Division of Cardiology, Xuzhou Central Hospital, Xuzhou Clinical School of Nanjing Medical University, Xuzhou Institute of Cardiovascular Disease, Xuzhou, Jiangsu, China;

关键词: Exosomes;    Mesenchymal stem cells;    miR-214-3p;    PTEN;    Myocardial infarction;   

DOI  :  10.1186/s40824-023-00410-w

 received in 2023-04-01, accepted in 2023-07-02,  发布年份 2023

来源: Springer

【 摘 要 】

AimsExosomes are known as nanovesicles that are naturally secreted, playing an essential role in stem-mediated cardioprotection. This study mainly focused on investigating if exosomes derived from miR-214 overexpressing mesenchymal stem cells (MSCs) show more valid cardioprotective ability in a rat model of acute myocardial infarction (AMI) and its potential mechanisms.MethodsExosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214OE-Exo) and then they were delivered to cardiomyocytes and endothelial cells in vitro under hypoxia and serum deprivation (H/SD) condition or in vivo in an acutely infarcted Sprague-Dawley rat heart. Regulated genes and signal pathways by miR-214OE-Exo treatment were explored using western blot analysis and luciferase assay.Results in vitro, miR-214OE-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214OE-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214OE-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214OE-Exo accelerated angiogenesis in peri-infarct region. Mechanistically, we identified that exosomal miR-214-3p promoted cardiac repair via targeting PTEN and activating p-AKT signal pathway.ConclusionExosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function.Graphical abstract

【 授权许可】

CC BY   
© The Korean Society for Biomaterials 2023

【 图 表 】

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