RT Journal Article
SR Electronic
T1 Liver-Chip: Reproducing Human and Cross-Species Toxicities
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 631002
DO 10.1101/631002
A1 Kyung-Jin Jang
A1 Monicah A. Otieno
A1 Janey Ronxhi
A1 Heng-Keang Lim
A1 Lorna Ewart
A1 Konstantia Kodella
A1 Debora Petropolis
A1 Gauri Kulkarni
A1 Jonathan E. Rubins
A1 David Conegliano
A1 Janna Nawroth
A1 Damir Simic
A1 Wing Lam
A1 Monica Singer
A1 Erio Barale
A1 Bhanu Singh
A1 Manisha Sonee
A1 Anthony J. Streeter
A1 Carl Manthey
A1 Barry Jones
A1 Abhishek Srivastava
A1 Linda C. Andersson
A1 Dominic Williams
A1 Hyoungshin Park
A1 Riccardo Barrile
A1 Josiah Sliz
A1 Anna Herland
A1 Suzzette Haney
A1 Katia Karalis
A1 Donald E. Ingber
A1 Geraldine A. Hamilton
YR 2019
UL http://biorxiv.org/content/early/2019/05/15/631002.abstract
AB Nonclinical rodent and non-rodent 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 Organ-on-Chip (Organ-Chip) technology to design rat, dog, and human Liver-Chips 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-Chips detected diverse phenotypes of liver toxicity including hepatocellular injury, steatosis, cholestasis, and fibrosis as well as species-specific toxicities when treated with tool compounds. Multi-species Liver-Chips 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.One Sentence Summary Microengineered Organ-Chip technology has been used to design rat, dog and human Liver-Chips that recapitulate species-specific liver toxicities.