Transplantation of Cardiac Mesenchymal Stem Cell-Derived Exosomes for Angiogenesis.

Chengwei Ju,Jingwen Cai,Youngjun Li,Yaoliang Tang,Yutao Liu,Naifeng Liu,Yan Shen,Gengshan Ma

doi:10.1007/s12265-018-9824-y

Abstract

We demonstrated the effects of exosomes secreted by cardiac mesenchymal stem cells (C-MSC-Exo) in protecting acute ischemic myocardium from reperfusion injury. To investigate the effect of exosomes from C-MSC on angiogenesis, we injected C-MSC-Exo or PBS intramuscularly into ischemic hind limb. Blood perfusion of limb was evaluated by laser Doppler Imaging. We observed that ischemic limb treated with C-MSC-Exo exhibits improved blood perfusion compared to ischemic limb treated with PBS at 2weeks and 1month after induction of limb ischemia. To explore the potential mechanisms underlying C-MSC-Exo's angiogenetic effect, we performed microRNA array analysis and identify mmu-miR-7116-5p as the most abundant enriched miRNA detected in C-MSC-Exo. Bioinformatics' analysis shows that miR-7116-5p negatively regulates protein polyubiquitination. In conclusion, our study demonstrated that intramuscular delivery of C-MSC-Exo after limb ischemia improves blood perfusion, and we identified the most abundant miRNAs that are preferentially enriched in C-MSC-Exo.

Highlights

Ischemic heart disease is the leading cause of death in the developed and developing countries[1]
We have reported that cardiac mesenchymal stem cells (C-MSCs) secretes exosomes that have paracrine effects to protect ischemic myocardium from apoptosis induced by acute myocardial ischemia/reperfusion [19]
These data indicate that C-MSCs represent a subpopulation of cardiac-derived mesenchymal stem cells

Summary

Introduction

Ischemic heart disease is the leading cause of death in the developed and developing countries[1]. The progressive apoptosis of cardiomyocytes exacerbates adverse left ventricular remodeling and promotes the progress of chronic heart failure[5]. Stem cells have the potential for promoting heart repair. Endothelial progenitor cells (EPCs) have been shown to protect ischemic myocardium via angiogenesis and vasculogenesis[9]. There are cardiac mesenchymal stem cells (C-MSCs) in the adult heart[10]. Our previous studies showed that transplantation of bone marrow derived MSCs promotes cardiac angiogenesis through paracrine effects [16, 17]. Since cultured stem cells are at risk of tumorigenesis for clinical application [18], we want to determine if the non-cellular, paracrine fraction of C- MSCs can be used for angiogenesis

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Conclusion