Disease modeling of pulmonary fibrosis using human iPS cell-derived alveolar organoids (SPC+ cells)

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 observed in pulmonary fibrosis. CPMhigh progenitor cells were differentiated from iPSCs. CPMhigh progenitor cells and human fetal lung fibroblasts 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 each reagent was washed out and the organoids were incubated for another 3 days. SPC+ cells in each condition were isolated from alveolar organoids on day17.