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J Vis Exp. 2018 May 19;(135). doi: 10.3791/57194.

Using Human Induced Pluripotent Stem Cell-derived Hepatocyte-like Cells for Drug Discovery.

Author information

1
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina.
2
Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina; duncanst@musc.edu.

Abstract

The ability to differentiate human induced pluripotent stem cells (iPSCs) into hepatocyte-like cells (HLCs) provides new opportunities to study inborn errors in hepatic metabolism. However, to provide a platform that supports the identification of small molecules that can potentially be used to treat liver disease, the procedure requires a culture format that is compatible with screening thousands of compounds. Here, we describe a protocol using completely defined culture conditions, which allow the reproducible differentiation of human iPSCs to hepatocyte-like cells in 96-well tissue culture plates. We also provide an example of using the platform to screen compounds for their ability to lower Apolipoprotein B (APOB) produced from iPSC-derived hepatocytes generated from a familial hypercholesterolemia patient. The availability of a platform that is compatible with drug discovery should allow researchers to identify novel therapeutics for diseases that affect the liver.

PMID:
29863663
PMCID:
PMC6101263
[Available on 2019-05-19]
DOI:
10.3791/57194
[Indexed for MEDLINE]

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