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World J Stem Cells. Sep 26, 2016; 8(9): 297-305
Published online Sep 26, 2016. doi: 10.4252/wjsc.v8.i9.297
Stem cell-derived exosomes as a therapeutic tool for cardiovascular disease
Etsu Suzuki, Daishi Fujita, Masao Takahashi, Shigeyoshi Oba, Hiroaki Nishimatsu
Etsu Suzuki, Institute of Medical Science, St. Marianna University School of Medicine, Miyamae-ku, Kawasaki 216-8512, Japan
Daishi Fujita, Masao Takahashi, Shigeyoshi Oba, Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
Hiroaki Nishimatsu, Department of Urology, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan
Author contributions: Suzuki E, Fujita D, Takahashi M, Oba S and Nishimatsu H equally contributed to this paper with conception and design of the study, literature review, and drafting this paper.
Conflict-of-interest statement: There exist no conflicts of interest in this study.
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: Etsu Suzuki, MD, PhD, Institute of Medical Science, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki 216-8512, Japan. esuzuki-tky@umin.ac.jp
Fax: +81-044-9778361
Received: May 26, 2016
Peer-review started: May 27, 2016
First decision: July 6, 2016
Revised: July 12, 2016
Accepted: July 20, 2016
Article in press: July 22, 2016
Published online: September 26, 2016
Abstract

Mesenchymal stem cells (MSCs) have been used to treat patients suffering from acute myocardial infarction (AMI) and subsequent heart failure. Although it was originally assumed that MSCs differentiated into heart cells such as cardiomyocytes, recent evidence suggests that the differentiation capacity of MSCs is minimal and that injected MSCs restore cardiac function via the secretion of paracrine factors. MSCs secrete paracrine factors in not only naked forms but also membrane vesicles including exosomes containing bioactive substances such as proteins, messenger RNAs, and microRNAs. Although the details remain unclear, these bioactive molecules are selectively sorted in exosomes that are then released from donor cells in a regulated manner. Furthermore, exosomes are specifically internalized by recipient cells via ligand-receptor interactions. Thus, exosomes are promising natural vehicles that stably and specifically transport bioactive molecules to recipient cells. Indeed, stem cell-derived exosomes have been successfully used to treat cardiovascular disease (CVD), such as AMI, stroke, and pulmonary hypertension, in animal models, and their efficacy has been demonstrated. Therefore, exosome administration may be a promising strategy for the treatment of CVD. Furthermore, modifications of exosomal contents may enhance their therapeutic effects. Future clinical studies are required to confirm the efficacy of exosome treatment for CVD.

Keywords: Exosomes, Messenger RNA, Cardiovascular disease, Mesenchymal stem cells, Stem cells, MicroRNA

Core tip: Exosomes are membrane vesicles that contain and transport specific bioactive molecules, such as proteins, messenger RNAs, and microRNAs, to recipient cells. In this review, we describe the mechanisms of exosome biogenesis, selective sorting of bioactive molecules into exosomes, and exosome secretion. We also discuss preclinical studies in which stem cell-derived exosomes were successfully used to treat cardiovascular disease (CVD). Finally, we discuss the future possibility of exosome-based clinical treatment of CVD.