Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes Promotes Repair in Ischemic Myocardium.

Chengwei Ju,Il-man Kim,Jingwen Cai,Yaoliang Tang,Yutao Liu,Neal L. Weintraub,Gengshan Ma,Yan Shen,Naifeng Liu

doi:10.1007/s12265-018-9822-0

Abstract

Our previous study demonstrated the beneficial effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. Here, we investigated the effect of exosomes from C-MSC on angiogenesis in ischemic myocardium. We intramyocardially injected C-MSC-Exo or PBS into the infarct border zone after induction of acute mouse myocardial infarction (MI). We observed that hearts treated with C-MSC-Exo exhibit improved cardiac function compared to control hearts treated with PBS at one month after MI. Capillary density and Ki67-postive cells were significantly higher following treatment with C-MSC-Exo as compared with PBS. Moreover, C-MSC-Exo treatment increased cardiomyocyte proliferation in infarcted hearts. In conclusion, intramyocardial delivery of C-MSC-Exo after myocardial infarction enhances cardiac angiogenesis, promotes cardiomyocyte proliferation, and preserves heart function. C-MSC-Exo constitute a novel form of cell-free therapy for cardiac repair.

Highlights

Ischemic heart disease is a leading cause of morbidity and mortality worldwide[1], in part because the adult heart has only very limited capacity to regenerate or repair itself [2]
In this study, we found that injection of cardiac mesenchymal stem cells (C-MSC)-Exo into ischemic myocardium promotes angiogenesis, stimulates the proliferation of cardiomyocytes, and preserves heart function post-myocardial infarction (MI)
Our findings support the growing body of evidence suggesting that MSC transplantation promotes heart repair through diverse paracrine effects[43]

Summary

Introduction

Ischemic heart disease is a leading cause of morbidity and mortality worldwide[1], in part because the adult heart has only very limited capacity to regenerate or repair itself [2]. This results in a cascade of left ventricular remodeling, cardiomyopathy, and eventually chronic heart failure[3]. Numerous studies have demonstrated that mesenchymal stem cells can release angiogenetic cytokines, such as VEGF, bFGF, and SDF-1α, to promote angiogenesis in ischemic myocardium, one potential mechanism of paracrine heart repair[13, 14]

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