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Status and Use of Induced Pluripotent Stem Cells (iPSCs) in Toxicity Testing

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Drug-Induced Liver Toxicity

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Adverse drug reactions (ADRs) are a major cause of drug attrition during development and withdrawal from market. Hepatotoxicity is among the most common reasons given for drug attrition or withdrawal; this occurs for a multitude of reasons among which is certainly the lack of adequate models able to recapitulate hepatotoxicity in vitro. The loss of compounds in late-stage testing or after marketing is a major financial burden for the pharmaceutical industry and improved models capable of predicting human toxicity of novel compounds at the early stages of testing are highly sought-after. An ideal novel hepatotoxicity model of should be amenable to high-throughput screening and able to recapitulate the hepatic phenotype over an extended period and also model idiosyncratic drug-induced liver injury (DILI). There are no currently models able to fulfill these requirements.

Pluripotent stem cell-derived hepatocyte-like cells (PSC-HLCs) are a developing model which show promise for hepatotoxicity testing. However, the current phenotype of PSC-HLCs is closer to a fetal hepatocyte than an adult hepatocyte. The methodologies for generating mature PSC-HLCs close to an idealized hepatotoxicity model remain to be developed, though incremental improvements to the state-of-the-art are frequently made. Novel PSC-HLC technologies are being developed independently in many research groups; as such there is a need for standardization in benchmarking of these cells and for evaluating the performance and functionality of newly developed HLC models.

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Author notes

  1. Min Wei Wong and Chris S. Pridgeon contributed equally to this work.

Authors and Affiliations

  1. Department of Molecularand Clinical Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, UK

    Min Wei Wong, Chris S. Pridgeon, Constanze Schlott, B. Kevin Park & Christopher E. P. Goldring

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  1. Min Wei Wong
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  2. Chris S. Pridgeon
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  3. Constanze Schlott
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  4. B. Kevin Park
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  5. Christopher E. P. Goldring
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Correspondence to Christopher E. P. Goldring .

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Editors and Affiliations

  1. Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR, USA

    Minjun Chen

  2. Drug Safety Research and Development, Pfizer Inc., Groton, CT, USA

    Yvonne Will

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Wong, M.W., Pridgeon, C.S., Schlott, C., Park, B.K., Goldring, C.E.P. (2018). Status and Use of Induced Pluripotent Stem Cells (iPSCs) in Toxicity Testing. In: Chen, M., Will, Y. (eds) Drug-Induced Liver Toxicity. Methods in Pharmacology and Toxicology. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-7677-5_10

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