Staged Construction of Pluripotent Stem Cell Lung Models for Assessing Respiratory Toxicity of Environmental Pollutants

Due to factors such as smoking, air pollution, and an aging population, the prevention and control of chronic respiratory diseases in China are becoming more severe. Combining current epidemiological investigations, exposure to environmental pollutants such as atmospheric pollutants, persistent organic pollutants, and heavy metals may have adverse effects on lung development. Lung differentiation models are crucial tools for elucidating the process of lung development. Through the combined effect of various cell growth factors and small molecules, pluripotent stem cells are successively induced to the definitive endoderm, the anterior foregut endoderm, lung progenitor cells, and alveolar epithelial cells and eventually form matured lung alveolar organoids, revealing the complex mechanisms of lung tissue formation. This Review compares various differentiation schemes based on in vitro culture protocols and conducts in-depth discussions for the current research on the toxicity of environmental pollutants using lung differentiation models. It aims to offer model selection criteria for scientists with different research purposes and provide scientific evidence to further research the impact of environmental pollution on respiratory diseases, as well as to provide important references for protecting public health.