Recent Applications of Lung Organoid and Lung-on-a-Chip Technologies for Evaluating the Toxicity of Fine Particulate Matter.

There is mounting epidemiologic and experimental evidence of the harmful effects of exposure to fine particulate matter (PM2.5) on human lung health. However, the current utilization of in vitro two-dimensional (2D) cell culture and in vivo animal models falls short in accurately recapitulating the complexity, functions, and development of the human lung. Recently, technologies for creating 3D biomimetic lung organoids from human tissue and pluripotent stem cells that mimic the structure and function of human organs have been rapidly developed. Human lung organoids are currently being applied in various studies such as disease modeling, drug efficacy testing, and regenerative medicine. In the field of environmental toxicology, human lung organoids offer a promising solution for more accurately assessing the health impacts of exposure to PM2.5 and to the limitations posed by 2D cultures and animal models. In this review, we summarize the effects of PM2.5 exposure on human lung and other organoids, as well as the molecular and genetic impacts of such exposure using human organoids. Furthermore, the development of lung-on-a-chip technology to mimic the microenvironment and its utilization for evaluating the pulmotoxicity of PM2.5 exposure are discussed.