Human airway organoids as 3D in vitro models for a toxicity assessment of emerging inhaled pollutants: Tire wear particles

Abstract

Three-dimensional (3D) structured organoids have become increasingly promising and effective in vitro models, and there is an urgent need for reliable models to assess health effects of inhaled pollutants on the human airway. In our study, we conducted a toxicity assessment of human airway organoids (hAOs) for tire wear particles (TWPs) as an emerging inhaled pollutant. We induced primary human bronchial epithelial cells (HBECs) to generated human airway organoids, which recapitulated the key features of human airway epithelial cells including basal cells, ciliated cells, goblet cells, and club cells. TWPs generated from the wearing of tire treads were considered a major source of emerging inhaled road traffic-derived non-exhaust particles, but their health effect on the lungs is poorly understood. We used human airway organoids to assess the toxicology of tire wear particles on the human airway. In an exposure study, the inhibitory effect of TWPs on the growth of human airway organoids was observed. TWPs induced significant cell apoptosis and oxidative stress in a dose-dependent manner. From the qPCR analysis, TWPs significantly up-regulated the expression pf genes involved in the inflammation response. Additionally, the exposure of TWPs reduced SCGB1A1 gene expression associated with the function of the club cell and KRT5 gene expression related to the function of basal cells. In conclusion, this was first study using human airway organoids for a toxicological assessment of TWPs, and our findings revealed that human airway organoids provide an evaluation model of inhaled pollutants potentially affecting the lungs.

Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms

“…It has been documented that Notch signaling regulates stem cell maintenance and differentiation, cell proliferation, and apoptosis, which is necessary for maintaining the homeostasis of the adult lung following lung injury (120). In a study utilizing three-dimensional airway organoids, exposure to tire wire particles, which are trafficderived PM 10 , led to a reduction in the expression of SCGB1A1, a club cell marker, and CK5, a basal cell marker (121).…”

Organoids: The current status and biomedical applications

“…The lung toxicity of common air pollutants including benzo(a)pyrene, nano‐carbon black, and nano‐SiO2 has been assessed with human iPSC‐derived AT2‐like cell organoids 276 . Meanwhile, human airway organoids were employed as models for toxicological assessment of emerging inhaled pollutants of tire wear particles 277 . Nicotine exposure in pregnant women has been shown to cause harmful birth outcomes and effects on cerebral development 278 .…”

“… 276 Meanwhile, human airway organoids were employed as models for toxicological assessment of emerging inhaled pollutants of tire wear particles. 277 Nicotine exposure in pregnant women has been shown to cause harmful birth outcomes and effects on cerebral development. 278 Several studies have investigated the role of nicotine in abnormal human brain development and the potential mechanisms with organoid system models.…”

Transwell-based microphysiological platform for high-resolution imaging of airway tissues

“…During liquid aspiration from the channel, the perfusate was collected noninvasively from the system for secretome analysis of the apical tissue face. After the experiment, we recuperated the intact tissue model from the platform (7) to perform in-depth downstream analysis at tissue and single-cell level (8,9).…”

“…Along with this development, the use of transwell inserts has become increasingly popular to cultivate epithelial barrier structures in vitro. In these systems, airway tissues are cultured on a semipermeable membrane that enables the creation of a physiologically relevant air-liquid interface, establishing transwells as standard tools for permeability and transport studies across the epithelial barrier [4][5][6][7][8]. Moreover, transwells are easy to handle and well-suited for highthroughput applications due to their availability in various multi-well plate formats.…”