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Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Aug 26, 2018; 10(8): 106-115
Published online Aug 26, 2018. doi: 10.4252/wjsc.v10.i8.106
Stem cell-derived exosomes - an emerging tool for myocardial regeneration
Erzsebet Lazar, Theodora Benedek, Szilamer Korodi, Nora Rat, Jocelyn Lo, Imre Benedek
Erzsebet Lazar, Department of Internal Medicine, Clinic of Haematology and Bone Marrow Transplantation, University of Medicine and Pharmacy Tirgu Mures, Tirgu Mures 540042, Romania
Theodora Benedek, Szilamer Korodi, Nora Rat, Imre Benedek, Department of Internal Medicine, Clinic of Cardiology, University of Medicine and Pharmacy Tirgu Mures, Tirgu Mures 540136, Romania
Theodora Benedek, Szilamer Korodi, Nora Rat, Imre Benedek, Department of Advanced Research in Multimodality Cardiac Imaging, Cardio Med Medical Center, Tirgu Mures 540124, Romania
Jocelyn Lo, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States
Author contributions: All authors had full access to all the data in the study and take responsibility for the integrity of the data; Benedek T and Benedek I contributed to the study concept and design; Benedek T, Lazar E and Rat N contributed to the analysis and interpretation of data; Benedek T and Korodi S contributed to the drafting of the manuscript; Benedek I contributed to the critical revision of the manuscript for important intellectual content; all the authors have given final approval of the version to be published and agree to be accountable for all aspects of the work.
Supported by Research grant, No. 103544/2016 - PLaqueIMAGE, contract No. 26/01.09.2016, financed by the Romanian Ministry of European Funds, the Romanian Government and the European Union.
Conflict-of-interest statement: All authors declare no potential conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Theodora Benedek, MD, PhD, Full Professor, Department of Internal Medicine, Clinic of Cardiology, University of Medicine and Pharmacy Tirgu Mures, Gheorghe Marinescu Street No. 38, Tirgu Mures 540136, Romania. theodora.benedek@gmail.com
Telephone: +40-265-212111 Fax: +40-265-215768
Received: March 29, 2018
Peer-review started: March 30, 2018
First decision: April 23, 2018
Revised: July 11, 2018
Accepted: July 15, 2018
Article in press: July 16, 2018
Published online: August 26, 2018
Processing time: 150 Days and 23.6 Hours
Abstract

Cardiovascular diseases (CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction (AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cells that can generate new myocardial tissue to replace the damaged tissue. Stem cells (SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs (MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosome-based therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

Keywords: Acute myocardial infarction; Exosome; Stem cell; Cardiac regeneration; Cardiovascular diseases

Core tip: Regenerative therapy represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of infarcted tissue. Exosomes are small microvesicles released by living cells that act as miRNA nanocarriers, and exosomes can stimulate and modulate cellular proliferation and regeneration. Elevated exosome levels have been detected in human plasma in various cardiovascular diseases. Furthermore, myocardium-derived exosomes are potentially associated with myocardial healing. Given their paracrine properties, myocardium-derived exosomes have been proposed as a potential therapeutic option for myocardial regeneration. This review discusses the emerging roles of exosomes as candidate biomarkers and innovative therapies for cardiac regeneration.