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

Lookup NU author(s): Ivo Djidrovski, Dr Maria Georgiou, Marina MoyaMolina, Dr Git Chung, Professor Majlinda Lako, Professor Lyle Armstrong

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press.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.


Publication metadata

Author(s): Djidrovksi I, Georgiou M, Hughes GL, Patterson EI, Casas-Sanchez A, Penington SH, Biagini GA, Moya-Molina M, van den Bor J, Smit MJ, Chung G, Lako M, Armstrong L

Publication type: Article

Publication status: Published

Journal: Stem Cells

Year: 2021

Volume: 39

Issue: 10

Pages: 1310-1321

Print publication date: 01/10/2021

Online publication date: 21/06/2021

Acceptance date: 29/04/2021

Date deposited: 07/07/2021

ISSN (print): 1066-5099

ISSN (electronic): 1549-4918

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/stem.3422

DOI: 10.1002/stem.3422


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