Experimental Animals
Online ISSN : 1881-7122
Print ISSN : 1341-1357
ISSN-L : 0007-5124

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Organoid technology and lung injury mouse models evaluating effects of hydroxychloroquine on lung epithelial regeneration
Fuxiaonan ZHAOJianhai WANGQi WANGZhilli HOUYingchao ZHANGXue LIQi WUHuaiyong CHEN
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ジャーナル オープンアクセス 早期公開

論文ID: 21-0168

この記事には本公開記事があります。
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) damages lung epithelial stem/progenitor cells. Ideal anti-SARS-CoV-2 drug candidates should be screened to prevent secondary injury to the lungs. Here, we propose that in vitro three-dimensional organoid and lung injury repair mouse models are powerful models for the screening antiviral drugs. Lung epithelial progenitor cells, including airway club cells and alveolar type 2 (AT2) cells, were co-cultured with supportive fibroblast cells in transwell inserts. The organoid model was used to evaluate the possible effects of hydroxychloroquine, which is administered as a symptomatic therapy to COVID-19 patients, on the function of mouse lung stem/progenitor cells. Hydroxychloroquine was observed to promote the self-renewal of club cells and differentiation of ciliated and goblet cells in vitro. Additionally, it inhibited the self-renewal ability of AT2 cells in vitro. Naphthalene- or bleomycin-induced lung injury repair mouse models were used to investigate the in vivo effects of hydroxychloroquine on the regeneration of club and AT2 cells, respectively. The naphthalene model indicated that the proliferative ability and differentiation potential of club cells were unaffected in the presence of hydroxychloroquine. The bleomycin model suggested that hydroxychloroquine had a limited effect on the proliferation and differentiation abilities of AT2 cells. These findings suggest that hydroxychloroquine has limited effects on the regenerative ability of epithelial stem/progenitor cells. Thus, stem/progenitor cell-derived organoid technology and lung epithelial injury repair mouse models provide a powerful platform for drug screening, which could possibly help end the pandemic.

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© 2022 Japanese Association for Laboratory Animal Science

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