72 Chapter 4 ABSTRACT Chronic lung diseases result from alteration and/or destruction of lung tissue, inevitably causing decreased breathing capacity and quality of life for patients. While animal models have paved the way towards understanding pathobiology and developing therapeutic strategies for disease management, their translational capacity is limited. Therefore, the need for developing innovative in vitro models to reflect chronic lung diseases, facilitating mechanism investigation and advancement of new treatment strategies is well recognised. In the last decades, lungs, in healthy and diseased conditions, have been modelled using precision-cut lung slices, organoids, extracellular matrix-derived hydrogels and lung-on-chip systems. These three-dimensional models together provide a wide spectrum of applicability and mimicry of the lung microenvironment. While each system has its own limitations, their advantages over traditional two-dimensional culture systems, or even over animal models, increases the value of in vitro models. Generating new and advanced models with increased translational capacity will not only benefit our understanding of the pathobiology of lung diseases but should also quicken the timelines required for discovery and generation of new therapeutics. This article summarises and provides an outline of the European Respiratory Society (ERS) Research Seminar: “Innovative 3D models for understanding mechanisms underlying lung diseases: powerful tools for translational research” in Lisbon, Portugal in April 2022. Current in vitro models developed for recapitulating healthy and diseased lungs are outlined and discussed with respect to the challenges associated with them, efforts to develop best practices for model generation, characterisation and utilisation of models, as well as state-of-the-art translational potential.
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