Precision-cut tissue slices revisited: A classical method meets new challenges

The understanding of the underlying mechanisms of a potential drug safety liability and the prediction of a potential risk to man is important from a safety and regulatory perspective. Significant progress in molecular and cellular biology has lead to in vitro models being applied for this purpose. Precision-cut organ slices is an outstanding in vitro model, which maintains the in vivo tissue organization, contains all in vivo relevant cell types, architecture and functional heterogeneity. Historically, organ slice cultures have been applied to study drug metabolism, pharmacology, and compound toxicity. Recently, it has been used to provide information on immune and inflammatory responses, provide insight into pathways of organ injury, assess the involvement of specific cell types in toxicity, and differentiate between species specific responses, thus furthering our understanding in predicting human toxicities and their underlying mechanisms. We will review this latest state-of-the-art use of this technology by providing a forum for the users of precision-cut slices to share their experiences. Our panel of experts will discuss the strengths, opportunities, and limitations of the model to evaluate target organ toxicities. A focal point of our discussions will be the use of slice technology used as a predictive tool in drug development and bridging compound-related safety from different animal species to man. We will provide an overview of the innovative use of toxicity endpoints, functional markers, and demonstrate the use of the model for tailor-made assessment of mechanisms of drug-induced target organ toxicity.