Drug toxicology models by using hiPSC-derived alveolar organoids (AOs)

Microarray analysis was performed to obtain the transcriptomes of GNE7915-, amioarone- and vehicle control-treated hiPSC-derived SFTPC+ cells. AOs harboring SFTPC+ cells were generated from isolated CPMhigh cells by coculturing with human fetal lung fibroblasts. SFTPC+ cells were passaged in AOs. After passaged three times every two weeks, AOs were treated with 5 µM of GNE7915, 10 µM of amiodarone, or vehicle control (DMSO) for 10 days. SFTPC+ cells in each condition were isolated on Day 77 (n = 3 biological replicates).

为获取经GNE7915、胺碘酮（amiodarone）及溶剂对照处理的人类诱导多能干细胞（human induced pluripotent stem cell, hiPSC）衍生的SFTPC+细胞的转录组，本研究开展了微阵列分析。本研究通过将分离得到的CPMhigh细胞与人胎肺成纤维细胞共培养，构建了携带SFTPC+细胞的肺泡类器官（alveolar organoids, AOs）。SFTPC+细胞可在该类器官中传代培养。每两周传代一次、共传代三次后，将肺泡类器官分别用5 μM GNE7915、10 μM 胺碘酮及溶剂对照（二甲基亚砜，DMSO）处理10天。于第77天分离各处理组中的SFTPC+细胞，每组设置3次生物学重复。