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

被引：20

作者：

Zhu, Wenwu ^{[1
]}

Wang, Qingjie ^{[2
]}

Zhang, Jian ^{[3
]}

Sun, Ling ^{[2
]}

Hong, Xiu ^{[1
]}

Du, Wei ^{[1
]}

Duan, Rui ^{[1
]}

Jiang, Jianguang ^{[2
]}

Ji, Yuan ^{[2
]}

Wang, Haoran ^{[4
]}

Han, Bing ^{[1
]}

机构：

[1] Nanjing Med Univ, Xuzhou Cent Hosp, Xuzhou Inst Cardiovasc Dis, Xuzhou Clin Sch,Div Cardiol, Xuzhou, Jiangsu, Peoples R China

[2] Nanjing Med Univ, Affiliated Changzhou 2 Peoples Hosp, Dept Cardiol, Changzhou, Jiangsu, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Shanghai Inst Cardiovasc Dis, Shanghai Inst Med Imaging,Dept Echocardiog, Shanghai 200000, Peoples R China

[4] Nanjing Univ Chinese Med, Sch Pharm, Dept Pharmacol, Nanjing 210023, Peoples R China

来源：

BIOMATERIALS RESEARCH | 2023年 / 27卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Exosomes; Mesenchymal stem cells; miR-214-3p; PTEN; Myocardial infarction; MICRORNA-214; PROTECTS; DELIVERY; THERAPY; HEART; MODEL;

D O I：

10.1186/s40824-023-00410-w

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Aims Exosomes 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. Methods Exosomes were isolated from control MSCs (Ctrl-Exo) and miR-214 overexpressing MSCs (miR-214(OE)-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-214(OE)-Exo treatment were explored using western blot analysis and luciferase assay. Results in vitro, miR-214(OE)-Exo enhanced migration, tube-like formation in endothelial cells. In addition, miR-214(OE)-Exo ameliorated the survival of cardiomyocytes under H/SD. In the rat AMI model, compared to Ctrl-Exo, miR-214(OE)-Exo reduced myocardial apoptosis, and therefore reduced infarct size and improved cardiac function. Besides, miR-214(OE)-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. Conclusion Exosomes derived from miR-214 overexpressing MSCs have greatly strengthened the therapeutic efficacy for treatment of AMI by promoting cardiomyocyte survival and endothelial cell function. [GRAPHICS] .

引用

页数：15

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