Towards improved hepatocyte cultures: Progress and limitations

Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market. Therefore, there is an urgent need for reliable predictive in vitro tests, which unfailingly identify hepatotoxic drug candidates, reduce drug development time, expenses and the number of test animals. Currently,...

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Veröffentlicht in:Food and chemical toxicology 2020-04, Vol.138, p.111188, Article 111188
Hauptverfasser: Ruoß, Marc, Vosough, Massoud, Königsrainer, Alfred, Nadalin, Silvio, Wagner, Silvia, Sajadian, Sahar, Huber, Diana, Heydari, Zahra, Ehnert, Sabrina, Hengstler, Jan G., Nussler, Andreas K.
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Sprache:eng
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Zusammenfassung:Hepatotoxicity is among the most frequent reasons for drug withdrawal from the market. Therefore, there is an urgent need for reliable predictive in vitro tests, which unfailingly identify hepatotoxic drug candidates, reduce drug development time, expenses and the number of test animals. Currently, human hepatocytes represent the gold standard. However, the use of hepatocytes is challenging since the cells are not constantly available and lose their metabolic activity in culture. To solve these problems many different approaches have been developed in the past decades. The aim of this review is to present these approaches and to discuss the possibilities and limitations as well as future opportunities and directions. •Drug-induced liver injury is a major etiology of acute liver failure.•Human hepatocytes are the gold standard for in vitro testing of new drugs.•Currently, there are no techniques available to predict the hepatotoxicity of new drugs over a longer time period.•Promising approaches for prediction of hepatotoxicity in vivo exists but these need to be further improved in the future.
ISSN:0278-6915
1873-6351
DOI:10.1016/j.fct.2020.111188