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

IF 11.3 1区医学 Q1 Medicine

Biomaterials Research Pub Date : 2023-08-10 DOI:10.1186/s40824-023-00410-w

Wenwu Zhu, Qingjie Wang, Jian Zhang, Ling Sun, Xiu Hong, Wei Du, Rui Duan, Jianguang Jiang, Yuan Ji, Haoran Wang, Bing Han

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引用次数: 3

Abstract

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.

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来自过表达mir-214-3p的间充质干细胞的外泌体促进心肌修复。

目的:外泌体被称为自然分泌的纳米囊泡，在干细胞介导的心脏保护中起着重要作用。本研究主要探讨miR-214过表达的间充质干细胞(MSCs)衍生的外泌体是否在大鼠急性心肌梗死(AMI)模型中表现出更有效的心脏保护能力及其潜在机制。方法:从对照MSCs (control - exo)和miR-214过表达MSCs (mir - 214e - exo)中分离外泌体，在体外缺氧和血清剥夺(H/SD)条件下或急性梗死Sprague-Dawley大鼠心脏体内将其递送至心肌细胞和内皮细胞。采用western blot分析和荧光素酶法研究miR-214OE-Exo处理后的调控基因和信号通路。结果:在体外，miR-214OE-Exo增强了内皮细胞的迁移和管状形成。此外，miR-214OE-Exo改善H/SD下心肌细胞的存活。在大鼠AMI模型中，与Ctrl-Exo相比，miR-214OE-Exo减少了心肌凋亡，从而减少了梗死面积，改善了心功能。此外，miR-214OE-Exo可促进梗死周围区域的血管生成。在机制上，我们发现外泌体miR-214-3p通过靶向PTEN和激活p-AKT信号通路促进心脏修复。结论:miR-214过表达的MSCs衍生的外泌体通过促进心肌细胞存活和内皮细胞功能，大大增强了治疗AMI的疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials Research Medicine-Medicine (miscellaneous)

CiteScore

10.20

自引率

3.50%

发文量

审稿时长

30 days

期刊介绍： Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.