Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells

• Published in: Toxicology (Amsterdam) Vol. 387; pp. 1 - 9
• Main Authors: Kim, Dong Eon, Jang, Mi-Jin, Kim, Young Ran, Lee, Joo-Young, Cho, Eun Byul, Kim, Eunha, Kim, Yeji, Kim, Mi Young, Jeong, Won-il, Kim, Seyun, Han, Yong-Mahn, Lee, Seung-Hyo
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 15.07.2017
• Subjects: Acetaminophen - toxicity; Analgesics, Non-Narcotic - toxicity; Biological Assay; Cell Differentiation; Cell Survival - drug effects; Chemical and Drug Induced Liver Injury - etiology; Chemical and Drug Induced Liver Injury - immunology; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Cytokines - immunology; Cytokines - metabolism; Drug-induced liver injury; Embryonic Stem Cells - drug effects; Embryonic Stem Cells - immunology; Embryonic Stem Cells - metabolism; Embryonic Stem Cells - pathology; Emergency; Hepatocyte-kike cells derived from human embryonic stem cells; Hepatocytes - drug effects; Hepatocytes - immunology; Hepatocytes - metabolism; Hepatocytes - pathology; Human primary hepatocytes; Humans; Hypoglycemic Agents - toxicity; Immune cells. drug screening system; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Jurkat Cells; Phenotype; Pro- and anti- inflammatory cytokines; Risk Assessment; Thiazolidinediones - toxicity; Toxicity Tests - methods; APAP; DILI; thiazolidinedione; Pro- and anti- inflammatory cytokines; Hepatocyte-kike cells derived from human embryonic stem cells; primary human hepatocytes; PHHs; drug induced liver injury; interferon; hES-HLCs; hepatocyte-like cells derived from human embryonic stem cells; TNF; IFN; acetaminophen; hES-DE; definitive endoderm cells induced from hESCs; ΙL; tumor necrosis factor; Immune cells. drug screening system; Human primary hepatocytes; Drug-induced liver injury; interleukin; TZD
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2017.06.005

Highlights • Generation and characterization of hES-HLCs for evaluation of drug-induced immune cell-mediated hepatotoxicity. • The secretion of inflammatory cytokines is highly enhanced from APAP-treated hES-HLCs. • Immune cells are activated and produce pro-inflammatory cytokines by conditioned medium from hES-HLCs cultured with APAP. • Hepatotoxic results in hES-HLCs are consistent with those of primary human hepatocytes. • Hepatotoxicity of other drugs, such as TZD, is also validated with our drug screening system. • Non-hepatotoxic drugs such as aspirin and metformin do not induce the secretion of inflammatory cytokines from hES-HLCs