title: In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells.
abstract: Alcohol consumption has long been associated with a majority of liver diseases and has been found to influence both fetal and adult liver functions. In spite of being one of the major causes of morbidity and mortality in the world, currently, there are no effective strategies that can prevent or treat alcoholic liver disease (ALD), due to a lack of human-relevant research models. Recent success in generation of functionally active mature hepatocyte-like cells from human-induced pluripotent cells (iPSCs) enables us to better understand the effects of alcohol on liver functions. Here, we describe the method and effect of alcohol exposure on multistage hepatic cell types derived from human iPSCs, in an attempt to recapitulate the early stages of liver tissue injury associated with ALD. We exposed different stages of iPSC-induced hepatic cells to ethanol at a pathophysiological concentration. In addition to stage-specific molecular markers, we measured several key cellular parameters of hepatocyte injury, including apoptosis, proliferation, and lipid accumulation.
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Prasad
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yjang3@jhmi.edu.|Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. yjang3@jhmi.edu.|Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB2 Rm552, Baltimore, MD, 21231, USA. yjang3@jhmi.edu.
authors.forename: Yoon-Young
authors.initials: YY
authors.lastname: Jang
mesh_terms: D028341:Activins / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001391:Azo Compounds / Q000737:chemistry; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D065150:Cellular Reprogramming; D003094:Collagen / Q000737:chemistry; D004338:Drug Combinations; D000431:Ethanol / Q000494:pharmacology*; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007797:Laminin / Q000737:chemistry; D066292:Lipid Droplets / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D061251:Primary Cell Culture; D011509:Proteoglycans / Q000737:chemistry; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: D001391:Azo Compounds; D015415:Biomarkers; C473711:Chir 99021; D004338:Drug Combinations; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D011509:Proteoglycans; D011725:Pyridines; D011743:Pyrimidines; C422405:activin A; D028341:Activins; C059485:matrigel; D000431:Ethanol; D003094:Collagen; C011049:oil red O
keywords: Alcoholic liver disease; Apoptosis; Hepatic differentiation; Induced pluripotent stem cells; Liver steatosis