Translational models for acute respiratory injury and inflammation using precision cut lung slices

Research from basic science has remarkably changed the general perception of 3D organotypic tissue models. Precision cut lung slices (PCLS) display such a suitable ex vivo translational tissue model that maintains microanatomy and functionality of the respiratory tract. The model allows the investigation of effects of compounds and drugs directly on cytokine release and functional responses such as bronchoconstriction under similar experimental conditions in different species. The tissue can be stimulated with e.g. chemicals, lipopolysaccharides, bronchoconstricting agents and disease-related proteins. By this, different features of diseases such as asthma, COPD, and lung injury can be investigated. Depending on the underlying immunology, lipopolysaccharides and proteins such as IL-13 induce an acute increase of pro-inflammatory cytokines and/or airway hyperresponsiveness. Effects of chemicals were shown to correlate with in vivo inhalation toxicity studies. We found that the tissue response is highly comparable with the in vivo response. In summary, PCLS can be used as model to study several features of lung injury, COPD and asthma ex vivo. The different tissue responses can be used for the prediction of toxicological endpoints and adverse health outcomes such as organ injury, respiratory sensitization and inflammation. The presentation will give an overview about the current use of lung tissue in inhalation toxicology but also state their use for drug research.