The Optimal Intervention Time of Bone Marrow Mesenchymal Stem Cells in Ameliorating Cardiac Fibrosis Induced by Viral Myocarditis: A Randomized Controlled Trial in Mice.

Tingting Wu,Tianhe Xia,Xuliang Wang,Rongzhou Wu,Jing Huang,Ping Li,Yuan Xie,Hao Li,Feng Zhu,Lei Li,Yaoyao Yan

doi:10.1155/2017/3258035

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have recently been introduced to treat cardiovascular diseases, such as myocardial infarction and dilated cardiomyopathy. Nevertheless, there are few researches focused on the application of BMSCs in treating viral myocarditis, not to mention its optimal intervention timer potential mechanisms. In our study, we concentrated on finding an optimal time window to perform BMSCs treatment in a murine model of myocarditis induced by coxsackievirus B3 (CVB3). On the 1st day, 3rd day, 7th day, and 14th day after BALB/c mice were infected by CVB3, we intravenously injected equivalent BMSCs into the treatment groups. With a 28-day follow-up after inoculation, we found that the ventricular function was significantly improved in the BMSCs treatment group and cardiac fibrosis markedly ameliorated, especially when BMSCs were injected between 1 and 2 weeks after CVB3 inoculation. Furthermore, we demonstrated that after BMSCs treatment, the expressions of TGF-β, col1α1, and col3α1 were significantly decreased. Therefore, we conclude that BMSCs may have a potential to improve CVB3-induced myocarditis by ameliorating cardiac fibrosis through the inhibition of TGF-β expression.

Highlights

Viral myocarditis (VMC) is the inflammation of cardiac muscle which is mostly due to viral infection such as coxsackievirus B3 [1]
The thickness of the left ventricular anteroposterior wall attenuated at systolic and diastolic levels; the left ventricular internal diameter (LVIDs) at end-systole and the left ventricular end-systolic volume (LVESV) were significantly increased (q = 6.701, 7.052; P < 0 05)
After Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation, the levels of left ventricular ejection fraction (LVEF) and fractional shortening (FS) were significantly higher than those in the myocarditis group (P < 0 05), and the VMC1w + BMSCs and VMC2w + BMSCs subgroups had the most significant changes (q = 8.748, 8.428, 8.528, 8.190; P < 0 01). This suggested that BMSCs could significantly improve the cardiac function after 1-2 weeks of coxsackievirus B3 (CVB3) infection in mice

Summary

Introduction

Viral myocarditis (VMC) is the inflammation of cardiac muscle which is mostly due to viral infection such as coxsackievirus B3 [1]. The disease is characterized by persistent inflammation and loss of cardiomyocytes which are later gradually replaced by fibrosis [2] It is a selflimited infection in most patients [3], there are severe conditions, like sudden unexpected death and dilated cardiomyopathy (DCM) [4, 5]. Zhang et al uncovered that BMSCs could secrete exosomes to promote proliferation, migration, and tube formation of cardiac stem cells [13]. It suggested that BMSCs might create a suitable microenvironment for cardiac stem cells to differentiate into cardiomyocytes and vascular endothelial cells and participate in the repair of damaged myocardium. We found BMSCs ameliorated cardiac fibrosis and the optimal treatment time of BMSCs was 1-2 weeks after CVB3 inoculation

Materials and Methods

Results

Discussion