01755nas a2200241   4500000000100000000000100001008004100002260001500043653001900058653001800077653001900095653001500114100001600129700001400145700001300159700001500172245006900187856007200256300001000328490000800338520115300346022001401499       2023                            d  c2023-02-0110aIn vitro model10aLung organoid10aLung stem cell10aSARS-CoV-21 aWenhao Yang1 aYingna Li1 aFang Shi1 aHanmin Liu00aHuman lung organoid: Models for respiratory biology and diseases  uhttps://www.sciencedirect.com/science/article/pii/S0012160622002305  a26-340 v4943 aThe 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-β/BMP/SMAD, FGF and Wnt/β-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 biological features and pathophysiology of pulmonary diseases, especially COVID-19. Lung organoids provide an excellent in vitro model and research platform.  a0012-1606