Cell Toxicity Models
While the liver is an important site of toxicity, basic cellular toxicity studies are rarely performed in primary human hepatocytes. Such studies are most frequently performed very early in the drug development pipeline, with hepatic tumor cells lines.
However when liver toxicity becomes a specific concern because of animal model or phase I clinical trial results, then physiologically relevant human primary cell models become more important tools. For toxicity in vitro, our hepatocytes prequalified to be plateable for 5 days in culture are ideal. These include the General Purpose (HUCPG), Induction Qualified (HUCPI), and Transporter Qualified (HUCPQ) cells.
Building Complex Liver Toxicity Models
One type of toxicity that is detected only in current in vivo models is immune-mediate toxicity. In this case, inflammatory responses in liver lead to generation of reactive oxygen species which damage the hepatocytes. Over time, this mechanism can lead to liver failure. The ability now to create in vitro models that co-culture hepatocytes with Kupffer cells, the liver resident macrophage, can improve the ability to detect these complex toxicities early in development. Other new models such as co-cultures with stellate and liver endothelial cells, in both monolayer and 3D spheroid models, have been shown to increase the predictive power of cell culture models (9).