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. Overall design: 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.