Abstract
Air pollution is the leading environmental risk to human health. Toxicological studies indicate the toxic effects of air pollution on human disease according to in vitro cell lines and in vivo models. However, these evaluation tools have large uncertainties owing to the discrepancies of the in vivo microenvironment and species between these employed models and human. Recently, organoids have emerged as powerful tools for studying the impact of air pollution on health, including the mechanisms of particulate matter, novel pollutants inducing toxic injuries, and infectious diseases. Compared with animal models and conventional cell culture systems, organoids offer higher human relevance. However, the systematic methodological immaturity and potential challenges of organoids in air pollution research remain unclear. This review explored the potential of organoids on studying the health effects of air pollution, highlighting their advantages over traditional toxicological models and addressing the challenges that need to be overcome. We propose the future effort for developing organoid systems for air pollution exposure applications, incorporating environmental exposure biobank, microfluidic technologies, and gene editing tools, to further enhance toxicological predictive capabilities. These innovative approaches can gain deeper insights into the mechanisms of air pollution-induced toxic effects and broaden the applicability of organoids in environmental health.