Research Paper Volume 12, Issue 13 pp 12669—12683

Extracellular vesicles derived from microRNA-150-5p-overexpressing mesenchymal stem cells protect rat hearts against ischemia/reperfusion

Hesheng Ou1, *, , Hongli Teng1, *, , Yuwang Qin1, , Xuelan Luo2, , Peng Yang1, , Wenyu Zhang3, , Wei Chen4, , Dongning Lv5, , Huamin Tang6, ,

  • 1 Section of Science and Technology, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530201, P.R. China
  • 2 Research and Development Center of Zhuang and Yao Medicine, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530201, P.R. China
  • 3 Section of Drug and Equipment, The Central Hospital of China Railway 12th Bureau Group Co. Ltd, Taiyuan 030053, P.R. China
  • 4 Department of Pharmacy, Jinan Maternity and Child Care Hospital, Jinan 250001, P.R. China
  • 5 Section of Nephropathy, Pulmonary Diseases and Endocrinology, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530201, P.R. China
  • 6 Emergency First Aid Linkage Center, Guangxi International Zhuang Medicine Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530201, P.R. China
* Equal contribution

Received: July 17, 2019       Accepted: January 12, 2020       Published: July 13, 2020      

https://doi.org/10.18632/aging.102792
How to Cite

Copyright © 2020 Ou et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-interacting protein (TXNIP), which was then knocked-down to investigate its effects on myocardial remodeling, followed by detection on myocardial infarction size (MIS), myocardial collagen volume fraction (CVF) and cardiomyocyte apoptosis. MSCs-derived EVs carrying miR-150-5p were cultured with neonatal cardiomyocytes under hypoxia/hypoglycemia condition for in vitro exploration and intramyocardially injected into I/R rats for in vivo exploration. I/R-induced rats presented higher TXNIP levels and lower miR-150-5p levels, along with increased cardiomyocyte apoptosis. miR-150-5p in MSCs was transferred through EVs to cardiomyocytes, leading to suppressed myocardial remodeling, as reflected by smaller MIS and CVF and suppressed cardiomyocyte apoptosis. I/R-treated rats injected with MSCs-derived EVs containing miR-150-5p showed a reduction in myocardial remodeling associated with the downregulation of TXNIP, which may be clinically applicable for treatment of I/R.

Abbreviations

miRNAs: microRNAs; MSCs: Mesenchymal stem cells; I/R: ischemia/reperfusion; TXNIP: thioredoxin-interacting protein; CVF: collagen volume fraction; MIS: myocardial infarction size; MI: Myocardial infarction; MSCs: mesenchymal stem cells; SD: Sprague Dawley; DMEM: Dulbecco's Modified Eagle Medium; FBS: fetal bovine serum; ECG: electrocardiogram; LAD: left anterior descending.