Modeling of lung organoid-based fibrosis for testing the sensitivity of anti-fibrotic drugs

Pulmonary fibrosis models play crucial roles in research of pulmonary fibrosis and anti-fibrosis drug screening. Despite the establishment of several pulmonary fibrosis models including lung fibrosis animals, stem cell differentiation, pulmospheres and so on, the one that mimic the personalized native lung lacks. We here developed a lung organoid-based fibrosis (LOF) model from native lung tissue, and the potential of the LOFs for the sensitivity test of anti-fibrotic drugs was evaluated. Our results showed that the LOFs could be self-organized from the lung organoids and the fibroblasts derived from native lung tissue. Histochemical examination demonstrated that the LOFs were characteristic of pulmonary fibrosis in structure. Single-cell sequencing (SCS) further revealed that the cell clusters mimicked fibrotic process at cellular and molecular levels in the LOFs. Drug sensitivity test indicated that the LOFs could not only be used to evaluate the efficacy of anti-fibrotic drugs, but also display their toxicity. We demonstrate that the LOFs represent an efficient fibrotic model that mimics faithfully the personalized characteristics of native lung tissue.