肺纤维化
类有机物
诱导多能干细胞
生物
特发性肺纤维化
细胞外基质
间充质干细胞
纤维化
成纤维细胞
细胞生物学
干细胞
肌成纤维细胞
肺
病理
癌症研究
细胞培养
胚胎干细胞
医学
内科学
遗传学
基因
生物化学
作者
Takahiro Suezawa,Shuhei Kanagaki,Keita Moriguchi,Atsushi Masui,Kazuhisa Nakao,Masayasu Toyomoto,Katsuto Tamai,Ryuta Mikawa,Toyohiro Hirai,Koji Murakami,Masatoshi Hagiwara,Shimpei Gotoh
标识
DOI:10.1016/j.stemcr.2021.10.015
摘要
Although alveolar epithelial cells play a critical role in the pathogenesis of pulmonary fibrosis, few practical in vitro models exist to study them. Here, we established a novel in vitro pulmonary fibrosis model using alveolar organoids consisting of human pluripotent stem cell-derived alveolar epithelial cells and primary human lung fibroblasts. In this human model, bleomycin treatment induced phenotypes such as epithelial cell-mediated fibroblast activation, cellular senescence, and presence of alveolar epithelial cells in abnormal differentiation states. Chemical screening performed to target these abnormalities showed that inhibition of ALK5 or blocking of integrin αVβ6 ameliorated the fibrogenic changes in the alveolar organoids. Furthermore, organoid contraction and extracellular matrix accumulation in the model recapitulated the pathological changes observed in pulmonary fibrosis. This human model may therefore accelerate the development of highly effective therapeutic agents for otherwise incurable pulmonary fibrosis by targeting alveolar epithelial cells and epithelial-mesenchymal interactions.
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