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World J Stem Cells. Mar 26, 2021; 13(3): 208-220
Published online Mar 26, 2021. doi: 10.4252/wjsc.v13.i3.208
Mesenchymal stromal cell-dependent immunoregulation in chemically-induced acute liver failure
Jia-Hang Zhou, Xuan Lu, Cui-Lin Yan, Xin-Yu Sheng, Hong-Cui Cao
Jia-Hang Zhou, Xuan Lu, Cui-Lin Yan, Xin-Yu Sheng, Hong-Cui Cao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Hong-Cui Cao, Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Author contributions: Zhou JH contributed to the study design, data collection, and manuscript writing; Lu X, Yan CL and Sheng XY contributed to the data collection; Cao HC conducted the conception, design, and manuscript writing; All authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81971756; and Stem Cell and Translational Research from National Key Research and Development Program of China, No. 2016YFA0101001.
Conflict-of-interest statement: Th authors declare having 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong-Cui Cao, MD, PhD, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. hccao@zju.edu.cn
Received: October 6, 2020
Peer-review started: October 6, 2020
First decision: December 24, 2020
Revised: January 8, 2021
Accepted: February 15, 2021
Article in press: February 15, 2021
Published online: March 26, 2021
Abstract

Drug-induced liver injury (DILI), which refers to liver damage caused by a drug or its metabolites, has emerged as an important cause of acute liver failure (ALF) in recent years. Chemically-induced ALF in animal models mimics the pathology of DILI in humans; thus, these models are used to study the mechanism of potentially effective treatment strategies. Mesenchymal stromal cells (MSCs) possess immunomodulatory properties, and they alleviate acute liver injury and decrease the mortality of animals with chemically-induced ALF. Here, we summarize some of the existing research on the interaction between MSCs and immune cells, and discuss the possible mechanisms underlying the immuno-modulatory activity of MSCs in chemically-induced ALF. We conclude that MSCs can impact the phenotype and function of macrophages, as well as the differentiation and maturation of dendritic cells, and inhibit the proliferation and activation of T lymphocytes or B lymphocytes. MSCs also have immuno-modulatory effects on the production of cytokines, such as prostaglandin E2 and tumor necrosis factor-alpha-stimulated gene 6, in animal models. Thus, MSCs have significant benefits in the treatment of chemically-induced ALF by interacting with immune cells and they may be applied to DILI in humans in the near future.

Keywords: Mesenchymal stromal cell, Immune response, Drug-induced liver injury, Acute liver failure, Dendritic cell

Core Tip: Drug-induced liver injury (DILI) is a crucial cause of acute liver failure (ALF). Although mesenchymal stromal cells (MSCs) have not been applied to DILI in clinical trials, their efficacy has been proven in various animal models of chemically-induced ALF. Immune system disorders play key roles in chemically-induced ALF, and MSCs are able to regulate the immune system through soluble factors and cell-to-cell contact, and eventually improve liver damage. We, herein, discuss the immunomodulatory properties of MSCs in different animal models that mimic the pathology of DILI in humans.