Zhou Jia-Hang, Lu Xuan, Yan Cui-Lin, Sheng Xin-Yu, Cao Hong-Cui
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.
World J Stem Cells. 2021 Mar 26;13(3):208-220. doi: 10.4252/wjsc.v13.i3.208.
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.
药物性肝损伤（DILI）是指由药物或其代谢产物引起的肝损伤，近年来已成为急性肝衰竭（ALF）的重要原因。动物模型中化学诱导的ALF模拟了人类DILI的病理过程；因此，这些模型被用于研究潜在有效治疗策略的机制。间充质基质细胞（MSCs）具有免疫调节特性，可减轻急性肝损伤并降低化学诱导的ALF动物的死亡率。在此，我们总结了一些关于MSCs与免疫细胞相互作用的现有研究，并讨论了MSCs在化学诱导的ALF中免疫调节活性的潜在机制。我们得出结论，MSCs可影响巨噬细胞的表型和功能，以及树突状细胞的分化和成熟，并抑制T淋巴细胞或B淋巴细胞的增殖和激活。在动物模型中，MSCs对细胞因子如前列腺素E2和肿瘤坏死因子α刺激基因6的产生也具有免疫调节作用。因此，MSCs通过与免疫细胞相互作用在化学诱导的ALF治疗中具有显著益处，并且在不久的将来可能应用于人类DILI的治疗。
