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Combining stem cell-derived hepatocytes with impedance sensing to better predict human drug toxicity

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Original languageEnglish
JournalExpert opinion on drug metabolism & toxicology
Early online date20 Dec 2018
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Publication statusE-pub ahead of print - 20 Dec 2018

Abstract

Background: The liver plays a central role in human drug metabolism. To model drug metabolism the major cell type of the liver, the hepatocyte, is commonly used. Hepatocytes can be derived from human and animal sources, including pluripotent stem cells. Cell based models have shown promise in modelling human drug exposure. The time point assays used in those studies are normally ‘snap-shot’ in nature and do not provide the complete picture for human drug exposure.
Research design and methods: In these study we employ stem cell-derived hepatocytes and impedance sensing to model human drug toxicity. This impedance-based stem cell assay reports hepatotoxicity in real time after treatment with BMS-827278-01(BMS4) and BMS-835981-01(BMS5).
Results: Using Electric Cell-substrate Impedance Sensing (ECIS) we were able to accurately measure drug toxicity post-drug exposure in real time and more quickly than gold standard biochemical assays.
Conclusions: ECIS is robust and non-destructive methodology capable of monitoring human drug exposure with superior performance to current gold standard ‘snap shot’ assays. We believe that the methodology presented within this article could prove valuable in the quest to better predict off target effects of drugs in humans.

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