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Ex vivo models for asthma, COPD and lung injury in precision cut lung slices (PCLS)

: Sewald, Katherina; Braun, Armin

ALTEX Proceedings 3 (2014), No.1, pp.209, Abstract VI-1a-466
ISSN: 2194-0479
World Congress on Alternatives and Animal Use in the Life Sciences <9, 2014, Prag>
Fraunhofer ITEM ()

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 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 including human. The tissue can be stimulated with, e.g., chemicals, lipopolysaccharides, bronchoconstricting agents and disease-related proteins. 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 toxicity but also state their use for drug research.