Research ArticleDRUG TESTING

Reproducing human and cross-species drug toxicities using a Liver-Chip

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Science Translational Medicine  06 Nov 2019:
Vol. 11, Issue 517, eaax5516
DOI: 10.1126/scitranslmed.aax5516

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Spotting species-specific toxicity

Candidate drug testing using standard preclinical models cannot accurately predict which compounds are likely to cause drug-induced liver injury in humans. To improve selection of promising drug candidates, Jang et al. developed a Liver-Chip consisting of rat, dog, or human hepatocytes, endothelial cells, Kupffer cells, and stellate cells. Using the microfluidic chips, the authors confirmed mechanism of action of several known hepatotoxic drugs and an experimental compound. A second experimental compound that induced fibrosis in a rat Liver-Chip did not alter hepatocyte function in human chips, whereas a third compound demonstrated increased toxicity in a dog Liver-Chip. Results support using multispecies chips to identify species-specific differences in drug metabolism and toxicity.

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