Review
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2018; 24(23): 2427-2440
Published online Jun 21, 2018. doi: 10.3748/wjg.v24.i23.2427
Taking advantage of the potential of mesenchymal stromal cells in liver regeneration: Cells and extracellular vesicles as therapeutic strategies
Esteban Juan Fiore, Luciana María Domínguez, Juan Bayo, Mariana Gabriela García, Guillermo Daniel Mazzolini
Esteban Juan Fiore, Luciana María Domínguez, Juan Bayo, Mariana Gabriela García, Guillermo Daniel Mazzolini, Laboratory of Gene Therapy, Instituto de Investigaciones en Medicina Traslacional, CONICET-Universidad Austral, Buenos Aires 999071, Argentina
Author contributions: Fiore EJ collected the information, wrote manuscript and drawn the figures; Domínguez LM collected information and assembly the tables; Bayo J and García MG wrote and reviewed the manuscript critically; Mazzolini GD wrote, reviewed critically and final approval of manuscript; all authors approved the final version of the manuscript.
Conflict-of-interest statement: The authors indicate no potential conflicts 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: Guillermo Daniel Mazzolini, MD, PhD, Professor, Laboratory of Gene Therapy, Instituto de Investigaciones en Medicina Traslacional, CONICET-Universidad Austral, Av. Pte. Perón 1500 (B1629AHJ) Derqui-Pilar, Buenos Aires 999071, Argentina. gmazzoli@austral.edu.ar
Telephone: +54-230-4482618 Fax: +54-230-4482618
Received: April 13, 2018
Peer-review started: April 13, 2018
First decision: April 27, 2018
Revised: May 8, 2018
Accepted: June 2, 2018
Article in press: June 2, 2018
Published online: June 21, 2018
Abstract

Cell-based therapies for acute and chronic liver diseases are under continuous progress. Mesenchymal stem/stromal cells (MSCs) are multipotent cells able to migrate selectively to damaged tissue and contribute to its healing and regeneration. The MSC pro-regenerative effect occurs due to their immunomodulatory capacity and their ability to produce factors that promote cell protection and survival. Likewise, it has been observed that part of their paracrine effect is mediated by MSC-derived extracellular vesicles (EVs). EVs contain proteins, lipids and nucleic acids (DNA, mRNA, miRNA, lncRNA) from the cell of origin, allowing for intercellular communication. Recently, different studies have demonstrated that MSC-derived EVs could reproduce, at least in part, the biological effects obtained by MSC-based therapies. Moreover, due to EVs’ stability for long periods of time and easy isolation methods they have become a therapeutic option to MSCs treatments. This review summarizes the latest results achieved in clinical trials using MSCs as cell therapy for liver regeneration, the role of EVs in liver physiopathology and the potential of MSCderived EVs as intercellular mediators and therapeutic tools in liver diseases.

Keywords: Mesenchymal stem cells, Extracellular vesicles, Cirrhosis, Liver, Acute damage, Regeneration

Core tip: Cell-based therapies for acute and chronic liver diseases are very attractive strategies. In particular, mesenchymal stem/stromal cells (MSCs) are multipotent cells able to induce protective and pro-regenerative effects in different liver diseases. The mechanism through which MSCs support tissue regeneration is via secretion of paracrine factors, and solid evidence supports that part of these effects is mediated by extracellular vesicles (EVs). Therefore, EVs have become an attractive option in the research for new treatments in liver diseases.