Drug-induced liver injury is a major cause of late-stage clinical drug attrition, market withdrawal and acute liver failure. Prediction of clinical drug-induced liver damage is of paramount importance at the earliest possible stage of development, both economically and health-wise and still remains a major challenge in the industry. The general approach to toxicology involves complex in vivo studies, the use of experimental animals in pharmacology and toxicology dates back to the last century. However, these experiments are time-consuming, costly, raise animal welfare issues and the predictive accuracy of animal in vivo testing for human adverse health effects is often questionable. Nowadays, there is a growing need to reduce the use of experimental animals. In vitro, cell-based models are often used to investigate preclinical hepatotoxicity. Due to differences in toxicity response of different species, the use of human cell lines is advisable. In in vitro models primary human hepatocytes, immortalized human hepatic cell lines have been used, but limited by viability, hepatic gene expression and function. Of the many options, three-dimensional (3D) models and stem cell-derived models have also become areas of significant interest. Developing appropriate toxicological model systems is not an easy task, but will help the effectiveness of toxicological studies.
Our goal is to compare different in vitro toxicology models and to investigate their applicability.
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