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

Djidrovksi, Ivo, Georgiou, Maria, Hughes, Grant ORCID: https://orcid.org/0000-0002-7567-7185, Patterson, Ian ORCID: https://orcid.org/0000-0003-3465-0848, Casas Sanchez, Aitor, Pennington, Shaun ORCID: https://orcid.org/0000-0002-7160-6275, Biagini, Giancarlo ORCID: https://orcid.org/0000-0001-6356-6595, Moya-Molina, Marina, van den Bo, Jelle, Smit, Martine J., Chung, Git and Lako, Majlinda (2021) 'SARS-CoV-2 infects an upper airway model derived from induced pluripotent stem cells'. Stem Cells. (In Press)

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Abstract

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.

Item Type: Article
Subjects: QU Biochemistry > Cells and Genetics > QU 300 General works
QW Microbiology and Immunology > Viruses > QW 160 Viruses (General). Virology
WA Public Health > WA 105 Epidemiology
WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 505 Viral respiratory tract infections
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1002/stem.3422
Depositing User: Cathy Waldron
Date Deposited: 23 Jun 2021 12:58
Last Modified: 23 Jun 2021 12:58
URI: https://archive.lstmed.ac.uk/id/eprint/18123

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