Human lung organoid: Models for respiratory biology and diseases

The human respiratory system, consisting of the airway and alveoli, is one of the most complex organs directly interfaced with the external environment. The diverse epithelial cells lining the surface are usually the first cell barrier that comes into contact with pathogens that could lead to deadly pulmonary disease. There is an urgent need to understand the mechanisms of self-renewal and protection of these epithelial cells against harmful pathogens, such as SARS-CoV-2. Traditional models, including cell lines and mouse models, have extremely limited native phenotypic features. Therefore, in recent years, to mimic the complexity of the lung, airway and alveoli organoid technology has been developed and widely applied. TGF-beta/BMP/SMAD, FGF and Wnt/beta-catenin signaling have been proven to play a key role in lung organoid expansion and differentiation. Thus, we summarize the current novel lung organoid culture strategies and discuss their application for understanding the lung bio-logical features and pathophysiology of pulmonary diseases, especially COVID-19. Lung organoids provide an excellent in vitro model and research platform.

Automated summary

The human respiratory system is a complex organ that directly interacts with the external environment. The epithelial cells lining the surface are the first line of defense against pathogens that cause pulmonary diseases. Lung organoid technology has been developed as a way to mimic the complexity of the lung and has been widely used. Signaling pathways such as TGF-beta/BMP/SMAD, FGF, and Wnt/beta-catenin have been found to play a crucial role in the expansion and differentiation of lung organoids. This article summarizes the current strategies for culturing lung organoids and discusses their application in understanding the biological features and pathophysiology of pulmonary diseases, especially COVID-19. Lung organoids provide an excellent in vitro model and research platform.