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In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells

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Patient-Specific Induced Pluripotent Stem Cell Models

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1353))

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.

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Acknowledgements

This work was supported in part by grants from Maryland Stem Cell Research Funds (2010-MSCRFII-0101 and 2013-MSCRFII-0170 and 2014-MSCRFF-0655) and by NIH (R43 ES023514, R21AA020020).

Author information

Authors and Affiliations

  1. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Lipeng Tian & Neha Prasad

  2. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Yoon-Young Jang

  3. Cellular and Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Yoon-Young Jang

  4. Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB2 Rm552, Baltimore, MD, 21231, USA

    Yoon-Young Jang

Authors
  1. Lipeng Tian
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  2. Neha Prasad
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  3. Yoon-Young Jang
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Corresponding author

Correspondence to Yoon-Young Jang .

Editor information

Editors and Affiliations

  1. Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada

    Andras Nagy

  2. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

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© 2014 Springer Science+Business Media New York

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Tian, L., Prasad, N., Jang, YY. (2014). In Vitro Modeling of Alcohol-Induced Liver Injury Using Human-Induced Pluripotent Stem Cells. In: Nagy, A., Turksen, K. (eds) Patient-Specific Induced Pluripotent Stem Cell Models. Methods in Molecular Biology, vol 1353. Humana Press, New York, NY. https://doi.org/10.1007/7651_2014_168

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  • DOI: https://doi.org/10.1007/7651_2014_168

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3033-3

  • Online ISBN: 978-1-4939-3034-0

  • eBook Packages: Springer Protocols

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