Abstract
Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced. For this damaged alveolar model, we find that the inhibition of Wnt signaling via XAV939 substantially improves alveolar repair function and prevents subsequent pulmonary fibrosis. Thus, the proposed alveolar cell culture strategy exhibits potential for the identification of pathogenesis and therapeutics in basic and translational research.
Highlights
Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking
We aim to develop a standardized method for long-term HPAEpiC culture that can enable the establishment of a tissue-level alveolar model to recapitulate the air–liquid interface (ALI) environment, alveolar epithelial barrier integrity, pulmonary surfactant production, and cellular plasticity
We defined a small-molecule cocktail (SMC) medium, which was supplemented with Jagged-1 peptide (JAG-1), recombinant
Summary
Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced. For this damaged alveolar model, we find that the inhibition of Wnt signaling via XAV939 substantially improves alveolar repair function and prevents subsequent pulmonary fibrosis. Previous studies have investigated the mechanism of the SARS-CoV-2 infection[4,5], the identification of pathogenesis and effective therapeutic strategies remains a challenge because of limited cell sources[6,7].
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