Differential toxicity of water- and DMSO-extractable PM2.5 fractions in human alveolar organoids.

PM2.5 is a major air pollutant associated with the onset and exacerbation of various diseases. However, due to the lack of suitable experimental models, the damage caused by PM2.5 to the organism and its relationship with diseases remain poorly understood. This study aims to establish a toxicity exposure model for PM2.5 using human alveolar organoids (hALOs) and investigate the differences in alveolar damage caused by water-extractable fraction and DMSO-extractable fraction of PM2.5. The results revealed that PM2.5 induced morphological damage in hALOs in a dose- and time-dependent manner, with the DMSO-extractable fraction eliciting more severe damage than the water-extractable fraction. PM2.5-induced increases in ROS levels and cell death were associated with the observed morphological damage. During the damage process, we also observed a sustained decline in the number of AT2 cells within the organoids, accompanied by a slight increase in the number of AT1 cells, suggesting that AT2-to-AT1 transdifferentiation may be occurring. This study helps advance the application of in vitro 3D organoid models in toxicological research and facilitate a deeper integration of PM2.5 toxicology and pathology.