Human Liver Slices to Investigate Injury and Repair

Abstract

Abstract

Introduction:

Liver organ slices are a multicellular three-dimensional tissue model, relevant for defining the dose–response profile of drug-induced injury, and for demonstrating which is the more sensitive species to the injury. In this organotypic ex vivo model, tissue architecture is maintained, including the cell–cell and cell–matrix interactions to mimic in vivo function.

Materials and Methods:

Extending the tissue viability for up to 7 days in culture expands the use of this model for studying pathways of injury and repair after the multiple dosing of a drug. Gene expression profiles plus functional measurements and histopathology provide mechanistic information of drug action on key pathways that are causal to organ dysfunction and injury.

Discussion:

Liver toxicity, detected in the animal in vivo studies, can be reproduced in the liver slice model with animal tissue, and then compared with human liver slice drug response.

Conclusions:

This allows to define the relevance of the toxicity for humans and to define the drug concentration range that will induce the potential side effects in humans compared with that in animals, as well as to identify potential biomarkers of the side effect.