ArticleRespiratory research2023
Use of a pulmosphere model to evaluate drug antifibrotic responses in interstitial lung diseases.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Mechanosensing Pathways in the Progression of Pulmonary Fibrosis.Current opinion in biomedical engineering · 2025Article
- Cadmium exposure triggers vimentin phosphorylation via SIRT6-regulated AKT/PI3K signaling pathway in COPD.European journal of cell biology · 2025Article
- Review
- The evolution ofEuropean respiratory review : an official journal of the European Respiratory Society · 2024Review
- Alveolar Organoids in Lung Disease Modeling.Biomolecules · 2024Review
- Lung organoids as emerging models in idiopathic pulmonary fibrosis research: Current applications, challenges, and future directions.Therapeutic advances in respiratory diseaseReview
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundInterstitial lung diseases (ILD) encompass a heterogenous group of diffuse parenchymal lung disorders characterized by variable degrees of inflammation and fibrosis. Pretherapeutic clinical testing models for such diseases can serve as a platform to test and develop effective therapeutic strategies. In this study, we developed patient derived 3D organoid model to recapitulate the disease process of ILDs. We characterized the inherent property of invasiveness in this model and tested for antifibrotic responses with an aim to develop a potential platform for personalized medicine in ILDs.
methodsIn this prospective study, 23 patients with ILD were recruited and underwent lung biopsy. 3D organoid-based models (pulmospheres) were developed from the lung biopsy tissues. Pulmonary functioning testing and other relevant clinical parameters were collected at the time of enrollment and follow up visits. The patient derived pulmospheres were compared to normal control pulmospheres obtained from 9 explant lung donor samples. These pulmospheres were characterized by their invasive capabilities and responsiveness to the antifibrotic drugs, pirfenidone and nintedanib.
resultsInvasiveness of the pulmospheres was measured by the zone of invasiveness percentage (ZOI%). The ILD pulmospheres (n = 23) had a higher ZOI% as compared to control pulmospheres (n = 9) (516.2 ± 115.6 versus 54.63 ± 19.6 respectively. ILD pulmospheres were responsive to pirfenidone in 12 of the 23 patients (52%) and responsive to nintedanib in all 23 patients (100%). Pirfenidone was noted to be selectively responsive in patients with connective tissue disease related ILD (CTD-ILD) at low doses. There was no correlation between the basal pulmosphere invasiveness, response to antifibrotics, and FVC change (Δ FVC).
conclusionsThe 3D pulmosphere model demonstrates invasiveness which is unique to each individual subject and is greater in ILD pulmospheres as compared to controls. This property can be utilized to test responses to drugs such as antifibrotics. The 3D pulmosphere model could serve as a platform for the development of personalized approaches to therapeutics and drug development in ILDs and potentially other chronic lung diseases.
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