Advanced lung organoids for respiratory system and pulmonary disease modeling

Amidst the recent coronavirus disease 2019 (COVID-19) pandemic, respiratory system research has made remarkable progress, particularly focusing on infectious diseases. Lung organoid, a miniaturized structure recapitulating lung tissue, has gained global attention because of its advantages over other conventional models such as two-dimensional (2D) cell models and animal models. Nevertheless, lung organoids still face limitations concerning heterogeneity, complexity, and maturity compared to the native lung tissue. To address these limitations, researchers have employed co-culture methods with various cell types including endothelial cells, mesenchymal cells, and immune cells, and incorporated bioengineering platforms such as air-liquid interfaces, microfluidic chips, and functional hydrogels. These advancements have facilitated applications of lung organoids to studies of pulmonary diseases, providing insights into disease mechanisms and potential treatments. This review introduces recent progress in the production methods of lung organoids, strategies for improving maturity, functionality, and complexity of organoids, and their application in disease modeling, including respiratory infection and pulmonary fibrosis.