Lung fibrogenic microenvironment in mouse reconstitutes human alveolar structure and lung tumor

Autor: Ryo Miyata, Koichi Hasegawa, Toshi Menju, Akihiko Yoshizawa, Akira Watanabe, Toyohiro Hirai, Hiroshi Date, Atsuyasu Sato
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: iScience, Vol 25, Iss 9, Pp 104912- (2022)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.104912
Popis: Summary: 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 in 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.
Databáze: Directory of Open Access Journals