摘要：SummaryA mesenchymal cell activation is a hallmark event of pulmonary fibrosis. Alveolar type 2 (AT2) cells are progenitor cells that maintain alveolar homeostasis, and their damage is assumed to be an initiating event for pulmonary fibrosis. However, the interaction between the lung fibrogenic microenvironment and AT2 cell dynamics remains to be elucidated. Here, we report a unique role of the lung fibrogenic microenvironment, where cell type-specific tissue reconstruction is achieved by exogenous cell transplantation. We found that in the lung fibrogenic microenvironment the AT2 cell pool was depleted, whereas mesenchymal cells could promote intact AT2 cell proliferationin vitro. Furthermore, exogenously transplanted AT2 cells formed alveolar colonies and ameliorated pulmonary fibrosis. Exogenous tumor cells formed tumor nests with relevant histological and transcriptional properties. Human primary cells were adaptable to this microenvironment, facilitating epithelial cell-targeted therapy in pulmonary fibrosis and the establishment of patient-derived xenografts for precision medicine in lung cancer.Graphical abstractDisplay OmittedHighlights•Severe bleomycin-induced lung injury causes a significant AT2 cell loss•Mesenchymal cells in the fibrogenic lung supports AT2 cell proliferation•AT2 cell transplantation ameliorates bleomycin-induced pulmonary fibrosis•Novel orthotopic lung cancer models are established for patient-derived xenograftsCancer; Cell biology; Molecular physiology
