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Reproducing human and cross-species drug toxicities using a Liver-Chip
Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
Janssen Pharmaceut Res & Dev, Nonclin Safety, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
Emulate Inc, 27 Drydock Ave, Boston, MA 02210 USA..
Janssen Pharmaceut Res & Dev, Drug Metab & Pharmacokinet, 1400 Welsh & McKean Rd, Spring House, PA 19477 USA..
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2019 (English)In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 11, no 517, article id eaax5516Article in journal (Refereed) Published
Abstract [en]

Nonclinical rodent and nonrodent toxicity models used to support clinical trials of candidate drugs may produce discordant results or fail to predict complications in humans, contributing to drug failures in the clinic. Here, we applied microengineered Organs-on-Chips technology to design a rat, dog, and human Liver-Chip containing species-specific primary hepatocytes interfaced with liver sinusoidal endothelial cells, with or without Kupffer cells and hepatic stellate cells, cultured under physiological fluid flow. The Liver-Chip detected diverse phenotypes of liver toxicity, including hepatocellular injury, steatosis, cholestasis, and fibrosis, and species-specific toxicities when treated with tool compounds. A multispecies Liver-Chip may provide a useful platform for prediction of liver toxicity and inform human relevance of liver toxicities detected in animal studies to better determine safety and human risk.

Place, publisher, year, edition, pages
AMER ASSOC ADVANCEMENT SCIENCE , 2019. Vol. 11, no 517, article id eaax5516
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Clinical Medicine
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URN: urn:nbn:se:kth:diva-264338DOI: 10.1126/scitranslmed.aax5516ISI: 000495685900004PubMedID: 31694927Scopus ID: 2-s2.0-85074625182OAI: oai:DiVA.org:kth-264338DiVA, id: diva2:1373059
Note

QC 20191126. QC 20200109

Available from: 2019-11-26 Created: 2019-11-26 Last updated: 2020-01-09Bibliographically approved

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Herland, Anna

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