Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2022; 28(28): 3627-3636
Published online Jul 28, 2022. doi: 10.3748/wjg.v28.i28.3627
Therapeutic potential of mesenchymal stem cells in the treatment of acute liver failure
Carl Randall Harrell, Dragica Pavlovic, Valentin Djonov, Vladislav Volarevic
Carl Randall Harrell, Regenerative Processing Plant LLC, Palm Harbor, FL 34176, United States
Dragica Pavlovic, Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Valentin Djonov, Institute of Anatomy, University of Bern, Bern 3012, Switzerland
Vladislav Volarevic, Department of Medical Genetics and Microbiology and Immunology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac 34000, Serbia
Author contributions: Harrell CR, Djonov V and Volarevic V analyzed the data and wrote the manuscript; Pavlovic D designed and created figures and wrote the manuscript; All authors have read and approve the final manuscript.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
Corresponding author: Vladislav Volarevic, MD, Full Professor, Department of Medical Genetics and Microbiology and Immunology, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozara Markovica Street, Kragujevac 34000, Serbia.
Received: March 24, 2022
Peer-review started: March 24, 2022
First decision: April 25, 2022
Revised: May 8, 2022
Accepted: June 24, 2022
Article in press: June 24, 2022
Published online: July 28, 2022

Acute liver failure (ALF) is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease. Mesenchymal stem cells (MSCs) are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF. MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages, reduce production of inflammatory cytokines in T lymphocytes, suppress hepatotoxicity of natural killer T (NKT) cells and promote generation and expansion of immunosuppressive T, B and NKT regulatory cells in acutely inflamed liver. Due to their nano-sized dimension and lipid envelope, intravenously injected MSC-derived exosomes (MSC-Exos) may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes. Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver, suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF. In this review, we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.

Keywords: Mesenchymal stem cells, Acute liver failure, Therapy, Immunomodulation, Regeneration

Core Tip: Due to their potent immunoregulatory, angiomodulatory and hepatoprotective properties, mesenchymal stem cells and their exosomes suppress detrimental immune response, prevent apoptosis and promote survival of injured hepatocytes which results in an enhanced repair and regeneration of acutely injured liver.