When AOs with macrophages were exposed to sodium chromate for 24 h, the IC 50 value and nitric oxide production were higher than when the AOs were exposed alone. The cytotoxicity and nitric oxide release in AO cultured with macrophages were then investigated. ![]() When the correlations between iAECs 2D culture and AOs 3D culture were calculated using Pearson's correlation coefficient r value, the nine chemicals that caused a significant decrease of cell viability in 3D culture were found to be highly correlated in 2D culture. ![]() The AOs were exposed for 24 h to nine chemical substances, and IC 50 values of the nine chemicals were determined using MTT assay. SFTPC and AQP5 were expressed in the AOs, and mRNA levels of SOX9, NKX2.1, GATA6, HOPX, and ID2 were increased. HiPS cells were cultured for 14 days with differentiation medium corresponding to each step, and the iAECs-based AOs were maintained for another 14 days. In this study, we developed human induced pluripotent stem cell (hiPS) cell-derived AECs (iAECs) and the iAECs based organoids (AOs) for testing AEC toxicity after chemical exposure. Alveolar epithelial cells (AECs) are vulnerable to injury, which can result in epithelial hyperplasia, apoptosis, and chronic inflammation.
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