Organ Model: Liver
Application: Toxicology
Highlights
Researchers from AbbVie built rat and dog quad-culture Liver-Chips (hepatocytes + sinusoidal endothelial, Kupffer, and stellate cells) under physiological flow, validated one week of experimental window stability (monitoring albumin, LDH/AST, CYPs/FMO), and then dosed ABT-288. The chips reproduced in vivo, species-specific metabolism: dog chips showed much higher FMO-mediated N-oxide formation and modestly greater toxicity signals (↓albumin, ↑ALT/AST/LDH) than rat—differences that were not seen in liver microsomes or 2D hepatocytes.
Significance: animal-cell MPS models can capture species differences in metabolism-driven hepatotoxicity that conventional in vitro systems miss, providing a translational bridge that both builds confidence in human MPS readouts and can help interpret preclinical safety signals (potentially reducing animal use and de-risking First in Human decisions).
