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

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…

• A
  AstraZeneca
• DA
  Defense Advanced Research Projects Agency

  Award: W911NF-12-2-0036
• JB
  Janssen Biotech
• JP
  Janssen Pharmaceuticals