SARS‐CoV‐2 infects an upper airway model derived from induced pluripotent stem cells

• Published in: Stem cells (Dayton, Ohio) Vol. 39; no. 10; pp. 1310 - 1321
• Main Authors: Djidrovski, Ivo, Georgiou, Maria, Hughes, Grant L., Patterson, Edward I., Casas‐Sanchez, Aitor, Pennington, Shaun H., Biagini, Giancarlo A., Moya‐Molina, Marina, Bor, Jelle, Smit, Martine J., Chung, Git, Lako, Majlinda, Armstrong, Lyle
• Format: Journal Article Web Resource
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2021; Oxford University Press
• Subjects: Biocompatibility; Cell Line; Cellular manufacture; Cilia; COVID-19 - pathology; COVID-19 - virology; Cytokines; Cytokines - metabolism; Embryonic Stem Cells/Induced Pluripotent Stem Cells; Epithelial Cells - pathology; Epithelial Cells - virology; Epithelium; Humans; In vivo methods and tests; induced pluripotent stem cells; Induced Pluripotent Stem Cells - pathology; Infections; Inflammation Mediators - metabolism; Inserts; interleukins; lung; Lung - pathology; Lung - virology; Lungs; Models, Biological; Pluripotency; Respiratory tract; SARS-CoV-2 - physiology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Stem cells; Toxicity; Viral diseases; Virus Replication - physiology; lung; cytokines; induced pluripotent stem cells; interleukins
• ISSN: 1066-5099; 1549-4918
• DOI: 10.1002/stem.3422

As one of the primary points of entry of xenobiotic substances and infectious agents into the body, the lungs are subject to a range of dysfunctions and diseases that together account for a significant number of patient deaths. In view of this, there is an outstanding need for in vitro systems in which to assess the impact of both infectious agents and xenobiotic substances of the lungs. To address this issue, we have developed a protocol to generate airway epithelial basal‐like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways. Basal‐like cells generated in this study were cultured on transwell inserts to allow formation of a confluent monolayer and then exposed to an air‐liquid interface to induce differentiation into a pseudostratified epithelial construct with a marked similarity to the upper airway epithelium in vivo. These constructs contain the component cell types required of an epithelial model system, produce mucus and functional cilia, and can support SARS‐CoV‐2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways. This method offers a readily accessible and highly scalable protocol for the manufacture of upper airway models that could find applications in development of therapies for respiratory viral infections and the assessment of drug toxicity on the human lungs. We have developed a protocol to generate airway epithelial basal‐like cells from induced pluripotent stem cells, which simplifies the manufacture of cellular models of the human upper airways that are capable of supporting SARS‐CoV‐2 infection/replication and the secretion of cytokines in a manner similar to that of in vivo airways.