Development of human iPS cell-derived alveolar and airway models using micropatterning plate for SARS-CoV-2 research

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Advanced cell culture systems including human induced pluripotent stem (iPS) cells and organoids enable the generation of intricate structural and functional organ models in vitro. Application of these advanced cell culture systems to research on a wide range of diseases including infectious diseases is underway. Due to the impact of the coronavirus disease 2019 (COVID-19) pandemic, advanced cell culture systems in the virus research field are rapidly becoming popular. Respiratory models generated using human iPS cells and organoid technology are useful for analyzing respiratory cell responses caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there is still room for the development of an apical-out model, which is essential for simple virus infection experiments, and a model that can analyze host responses in the alveoli and airways. In this study, we developed human iPS cell-derived alveolar and airway models with an apical-out structure by using a micropatterning plate. In the alveolar model, we confirmed that this model contains abundant type II alveolar epithelial (AT2) cells, which are the target cells of SARS-CoV-2 in the alveoli. In the airway model, we confirmed that this model contains abundant ciliated cells, which are the target cells of SARS-CoV-2 in the airway. Using our alveolar and airway models, we can analyze the differences in infection efficiency and host response of each SARS-CoV-2 variant. We hope that the human iPS cell-derived alveolar and airway models generated using a micropatterning plate will be used to analyze not only SARS-CoV-2 but also a wide range of respiratory viruses.