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

  • Lipeng Tian
  • Neha Prasad
  • Yoon-Young JangEmail author
Protocol
Part of the Methods in Molecular Biology book series (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.

Keywords

Induced pluripotent stem cells Alcoholic liver disease Hepatic differentiation Liver steatosis Apoptosis 

Notes

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).

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Oncology, The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Institute for Cell EngineeringJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Cellular and Molecular Medicine Graduate ProgramJohns Hopkins University School of MedicineBaltimoreUSA
  4. 4.Department of Oncology, The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins University School of MedicineBaltimoreUSA

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