Donor-to-donor variability of a human three-dimensional bronchial epithelial model: A case study of cigarette smoke exposure

In this report, 3D differentiated bronchial epithelial cells from three donors were used to investigate donor-to-donor variability, with an aqueous extract of cigarette smoke (CS) used as the test substance. Ciliary function, cytokine secretion, and histopathology, which are affected by CS, were examined, and transcriptomic analysis was also performed. The results revealed that interleukin-8 secretion and oxidative stress-related gene expression were consistently altered for all donors; however, their amplitudes varied. Moreover, one of the donors showed unique responses to CS, suggesting that this donor was an outlier. This donor showed intrinsic differences in histology, cytokine secretion, and gene expression profile. Such donors may help evaluate potential toxicological concerns and aid our understanding of disease pathogenesis. Conversely, these donors may confound toxicological assessment and endpoint selection. Fit-for-purpose handling of inter-donor variability is warranted.PMID:35595035 | DOI:10.1016/j.tiv.2022.105391

Source: Toxicology in Vitro - May 20, 2022 Category: Toxicology Authors: Sakura Mori Kanae Ishimori Kazushi Matsumura Shinkichi Ishikawa Shigeaki Ito Source Type: research