Therapeutic potential of miR-133a-transfected bone marrow mesenchymal stem cell transplantation in improving cardiac function post-myocardial infarction

Yanglanduo Cao; Xiaohan Chen; Biao Cheng; Xuefei Tao; Wei Zhang; Yong Shi; Jie Gao; Minghuan Fu

doi:10.1186/s13019-025-03367-0

Journal of Cardiothoracic Surgery (Feb 2025)

Therapeutic potential of miR-133a-transfected bone marrow mesenchymal stem cell transplantation in improving cardiac function post-myocardial infarction

Yanglanduo Cao,
Xiaohan Chen,
Biao Cheng,
Xuefei Tao,
Wei Zhang,
Yong Shi,
Jie Gao,
Minghuan Fu

Affiliations

Yanglanduo Cao: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Xiaohan Chen: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Biao Cheng: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Xuefei Tao: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Wei Zhang: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Yong Shi: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Jie Gao: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China
Minghuan Fu: Department of Geriatric Cardiovascular Disease, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China

DOI: https://doi.org/10.1186/s13019-025-03367-0
Journal volume & issue: Vol. 20, no. 1
pp. 1 – 16

Abstract

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Abstract Objective The objective of this study is to examine the therapeutic efficacy of miR-133a-transfected bone marrow mesenchymal stem cells (BM-MSCs) in restoring damaged myocardium, reducing myocardial fibrosis, and improving cardiac function following myocardial infarction (MI). Methods Bone marrow mesenchymal stem cells (BM-MSCs) were transfected with miR-133a using lentivirus vectors, and the in vitro transfection efficiency was assessed. A rat MI animal model was established to examine the survival rate of miR-133a-transfected BM-MSCs in ischemic myocardium. The effects of miR-133a transfection on rat primary cardiac fibroblasts were evaluated both in vitro and in vivo. Results The experimental group had a significantly higher concentration of double-stranded DNA (dsDNA) compared to the control group. Fluorescent staining revealed an enhanced survival rate of MSCs in the miR-133a transfection group compared to controls. Additionally, the protein and gene expression of apoptosis-related indicators in the infarcted myocardium were lower in the experimental group compared to the control group. Following co-culture with rat primary cardiac fibroblasts, the miR-133a-transfected MSCs exhibited a significantly lower expression of myofibroblast-specific proteins and mRNA compared to controls. The levels of collagen I, connective tissue growth factor (CTGF) protein, and messenger RNA (mRNA) in the infarcted myocardium of rats transplanted with BM-MSCs transfected with miR-133a were significantly lower than those in the control group, and their left ventricular ejection fraction (LVEF) was significantly increased compared with the group that received unmodified BM-MSCs. Conclusion Our results demonstrate that miR-133a transfection following MI improves the survival rate of transplanted MSCs in ischemia-hypoxic myocardium, inhibits the transformation of cardiac fibroblasts into myofibroblasts, reduces myocardial fibrosis, and improves cardiac function following MI. This approach holds promise as a novel therapeutic strategy for myocardial repair.

Published in Journal of Cardiothoracic Surgery

ISSN: 1749-8090 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Surgery: Anesthesiology
Website: https://cardiothoracicsurgery.biomedcentral.com/

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