85 Innovative 3D models for understanding mechanisms underlying lung diseases: powerful tools for translational research CHALLENGES ASSOCIATED WITH 3D IN VITRO MODELS In vitro models including PCLS, organoids, lung ECM-derived hydrogels, and LOC are powerful methods for employment in the quest to decipher the in vivo status of lung diseases at the cellular and ECM level. A comprehensive overview of the challenges associated with the above-mentioned in vitro models is presented in Table 2. In addition to the challenges specific for each model, there are overarching challenges for in vitro models in general. As research using such models progresses, the materials utilised, methods applied, and outcomes tested also diversify. As one of the primary outcomes of the “ERS Research Seminar 2022: Innovative 3D models for understanding mechanisms underlying lung diseases: powerful tools for translational research”, the participants were invited to contribute to a discussion on defining best practices when using these models and resources to improve reporting and reproducibility of data generated with these models. The main take-home message from these discussions was the need for clear and detailed methodology sections when reporting outcomes and open communication. Additionally, several other important issues were highlighted. Best practices for handling patient samples: All participants were appreciative of the opportunities and importance of using precious human samples; however, the limitations of this practice were also recognised. The variability in the results caused by sample processing can be addressed by suggesting optimal windows of time between explanting of tissues and processing and clarity of methodologies for processing when working with human material [134]. Extensive information, about each protocol used by investigators, in the materials and methods sections would improve the potential for accurate comparisons to be made between different studies. Primary lung tissue material is generally seen as the optimal choice of source for cell and ECM material, but access to such primary tissue is limited and not equally distributed between research centres. Obtaining ethical board permissions to use the sparse human-sourced material is a challenge [135], and the establishment of local exchange networks has aided in tackling this. However, a European network currently does not exist, which limits optimal distribution of primary samples. Moreover, limited-to-no access to “true” healthy lung samples hinders how we can model truly “normal” tissues, resulting in potential bias in the data generated. Extensive descriptions of the details of obtaining and processing animal-sourced materials used in combination with patient-derived material for in vitro models would stimulate cumulative research. 4
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