Miyata Ryo, Hasegawa Koichi, Menju Toshi, Yoshizawa Akihiko, Watanabe Akira, Hirai Toyohiro, Date Hiroshi, Sato Atsuyasu
Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
iScience. 2022 Aug 11;25(9):104912. doi: 10.1016/j.isci.2022.104912. eCollection 2022 Sep 16.
A 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 proliferation . 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.
间充质细胞激活是肺纤维化的标志性事件。2型肺泡上皮细胞（AT2）是维持肺泡稳态的祖细胞，其损伤被认为是肺纤维化的起始事件。然而，肺纤维化微环境与AT2细胞动态之间的相互作用仍有待阐明。在此，我们报道了肺纤维化微环境的独特作用，即通过外源性细胞移植实现细胞类型特异性组织重建。我们发现，在肺纤维化微环境中，AT2细胞池减少，而间充质细胞可促进完整的AT2细胞增殖。此外，外源性移植的AT2细胞形成肺泡集落并改善肺纤维化。外源性肿瘤细胞形成具有相关组织学和转录特性的肿瘤巢。人原代细胞适应这种微环境，有助于肺纤维化的上皮细胞靶向治疗以及建立用于肺癌精准医学的患者来源异种移植模型。
