Disease modeling of pulmonary fibrosis using human iPS cell-derived alveolar organoids (fibroblasts)

We developed an in vitro model of pulmonary fibrosis using alveolar organoids, consisting of human induced pluripotent stem cell-derived alveolar epithelial cells and human lung fibroblasts. In this model, fibroblasts were activated by bleomysin (BLM) treatment in an epithelial cell-dependent manner simillar to the pathogenic mechanism of pulmonary fibrosis. CPMhigh progenitor cells were differentiated from iPSCs. CPMhigh progenitor cells and human fetal lung fibroblasts (HFLF) were cocultured to generate SPC+cells. SPC+ cell-derived alveolar organoids passaged 3 times were treated with DMSO or 3 μg/mL BLM from day 11 to day14, then washed out of BLM, and incubated for another 3 days. Co-cultured fibroblasts were isolated by negative selection of EpCAM+ cells from alveolar organoids. In fibroblast only culture, the cells were treated as in alveolar organoids and all cells were collected.