論文 - 詳細
| RRC ID | 68764 |
|---|---|
| 著者 | Suezawa T, Kanagaki S, Moriguchi K, Masui A, Nakao K, Toyomoto M, Tamai K, Mikawa R, Hirai T, Murakami K, Hagiwara M, Gotoh S. |
| タイトル | Disease modeling of pulmonary fibrosis using human pluripotent stem cell-derived alveolar organoids. |
| ジャーナル | Stem Cell Reports |
| Abstract |
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. |
| 巻・号 | 16(12) |
| ページ | 2973-2987 |
| 公開日 | 2021-12-14 |
| DOI | 10.1016/j.stemcr.2021.10.015 |
| PII | S2213-6711(21)00550-6 |
| PMID | 34798066 |
| PMC | PMC8693665 |
| MeSH | Alveolar Epithelial Cells / drug effects Alveolar Epithelial Cells / metabolism Alveolar Epithelial Cells / pathology* Bleomycin Cell Differentiation / drug effects Cellular Senescence Fibroblasts / drug effects Fibroblasts / metabolism Fibroblasts / pathology Humans Imidazoles / pharmacology Induced Pluripotent Stem Cells / pathology* Models, Biological* Organoids / pathology* Pulmonary Fibrosis / pathology* Quinoxalines / pharmacology Receptor, Transforming Growth Factor-beta Type I / antagonists & inhibitors Receptor, Transforming Growth Factor-beta Type I / metabolism Signal Transduction / drug effects Transforming Growth Factor beta1 / metabolism |
| IF | 6.032 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 26 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 585A1(HPS0354) 648A1(HPS0360) |