Cardioprotective microRNAs: Lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease

Abbas Shapouri Moghaddam; Jalil Tavakol Afshari; Seyed-Alireza Esmaeili; Ehsan Saburi; Zeinab Joneidi; Amir Abbas Momtazi-Borojeni

doi:10.1016/j.atherosclerosis.2019.03.016

Cardioprotective microRNAs: Lessons from stem cell-derived exosomal microRNAs to treat cardiovascular disease

Atherosclerosis. 2019 Jun:285:1-9. doi: 10.1016/j.atherosclerosis.2019.03.016. Epub 2019 Mar 23.

Authors

Abbas Shapouri Moghaddam¹, Jalil Tavakol Afshari¹, Seyed-Alireza Esmaeili², Ehsan Saburi³, Zeinab Joneidi⁴, Amir Abbas Momtazi-Borojeni⁵

Affiliations

¹ Department of Immunology, BuAli Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
² Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Department, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
³ Clinical Research Development Center, Imam Hasan Hospital, North Khorasan University of Medical Sciences, Bojnurd, Iran; Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
⁴ Department of Genetics and Molecular Medicine, Zanjan University of Medical Science, Iran.
⁵ Halal Research Center of IRI, FDA, Tehran, Iran; Nanotechnology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology, Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: momtaziaa921@mums.ac.ir.

PMID: 30939341
DOI: 10.1016/j.atherosclerosis.2019.03.016

Abstract

The stem cell-based therapy has emerged as a promising therapeutic strategy for treating cardiovascular ischemic diseases (CVIDs), such as myocardial infarction (MI). However, some important functional shortcomings of stem cell transplantation, such as immune rejection, tumorigenicity and infusional toxicity, have overshadowed stem cell therapy in the setting of cardiovascular diseases (CVDs). Accumulating evidence suggests that the therapeutic effects of transplanted stem cells are predominately mediated by secreting paracrine factors, importantly, microRNAs (miRs) present in the secreted exosomes. Therefore, novel cell-free therapy based on the stem cell-secreted exosomal miRs can be considered as a safe and effective alternative tool to stem cell therapy for the treatment of CVDs. Stem cell-derived miRs have recently been found to transfer, via exosomes, from a transplanted stem cell into a recipient cardiac cell, where they regulate various cellular process, such as proliferation, apoptosis, stress responses, as well as differentiation and angiogenesis. The present review aimed to summarize cardioprotective exosomal miRs secreted by transplanted stem cells from various sources, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and cardiac stem/progenitor cells, which showed beneficial modulatory effects on the myocardial infracted heart. In summary, stem cell-exosomal miRs, including miR-19a, mirR-21, miR-21-5p, miR-21-a5p, miR-22 miR-24, miR-26a, miR-29, miR-125b-5p, miR-126, miR-201, miR-210, and miR-294, have been shown to have cardioprotective effects by enhancing cardiomyocyte survival and function and attenuating cardiac fibrosis. Additionally, MCS-exosomal miRs, including miR-126, miR-210, miR-21, miR-23a-3p and miR-130a-3p, are found to exert cardioprotective effects through induction of angiogenesis in ischemic heart after MI.

Keywords: Cardiovascular ischemic disease; Heart; Myocardial infarction; microRNA.

Publication types

Review

MeSH terms

Animals
Cardiotonic Agents / therapeutic use
Cardiovascular Diseases / drug therapy*
Exosomes / genetics*
Exosomes / metabolism
Humans
MicroRNAs / metabolism
MicroRNAs / therapeutic use*
Stem Cells / metabolism
Stem Cells / ultrastructure

Substances

Cardiotonic Agents
MicroRNAs