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. Overall design: 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.