Mesenchymal stromal cell-dependent immunoregulation in chemically-induced acute liver failure

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.