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
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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.
期刊介绍：
Journal of Cardiothoracic Surgery is an open access journal that encompasses all aspects of research in the field of Cardiology, and Cardiothoracic and Vascular Surgery. The journal publishes original scientific research documenting clinical and experimental advances in cardiac, vascular and thoracic surgery, and related fields.
Topics of interest include surgical techniques, survival rates, surgical complications and their outcomes; along with basic sciences, pediatric conditions, transplantations and clinical trials.
Journal of Cardiothoracic Surgery is of interest to cardiothoracic and vascular surgeons, cardiothoracic anaesthesiologists, cardiologists, chest physicians, and allied health professionals.
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