Precision-cut lung slices

For improved prediction of chemical toxicity and adverse drug reactions as well as for safety assessment in line with the principle of the 3Rs, other models than animals are needed. The aim of the 3Rs principle is to avoid animal experiments altogether (replacement), to reduce the number of animals per experiment (reduction) and to keep animal distress to an absolute minimum (refinement). As an adverse outcome induced by an agent (such as a chemical or drug) can be linked to molecular initiation events, it is possible to investigate early events in the pathogenesis of acute and chronic respiratory diseases by measurement of key events at the cellular or tissue level.

Over the past years, Fraunhofer ITEM scientists have built up expertise to advance the discovery and safety of drugs and chemicals by the use of human tissue. First publications on this topic defined a new standardized approach for using lung tissue ex vivo to assess lung injury and inflammation. This approach was then used to develop disease-related models of asthma, COPD, fibrosis and infection. By using these disease models, it was possible to show for example how pharmaceutical immunosuppression can lead to an increased risk for infection with influenza. In this context, human lung tissue increases the predictive validity of disease models and provides a reference point that can be correlated with clinical symptoms. Nevertheless, integrating human tissue into research and development remains a significant challenge.