Sars-Cov-2 Infects an Upper Airway Model Derived from Induced Pluripotent Stem Cells
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- Ivo Djidrovski
- Newcells Biotech Ltd, The Biosphere, Newcastle upon Tyne, UK
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- Maria Georgiou
- Biosciences Institute, Newcastle University, The International Centre for Life, Newcastle upon Tyne, UK
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- Grant L. Hughes
- Centre for Drugs and Diagnostics The Liverpool School of Tropical Medicine, Liverpool, Merseyside, UK
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- Edward I. Patterson
- Centre for Drugs and Diagnostics The Liverpool School of Tropical Medicine, Liverpool, Merseyside, UK
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- Aitor Casas-Sanchez
- Centre for Drugs and Diagnostics The Liverpool School of Tropical Medicine, Liverpool, Merseyside, UK
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- Shaun H. Pennington
- Centre for Drugs and Diagnostics The Liverpool School of Tropical Medicine, Liverpool, Merseyside, UK
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- Giancarlo A. Biagini
- Centre for Drugs and Diagnostics The Liverpool School of Tropical Medicine, Liverpool, Merseyside, UK
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- Marina Moya-Molina
- Newcells Biotech Ltd, The Biosphere, Newcastle upon Tyne, UK
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- Jelle Bor
- Vrije Universiteit Amsterdam Faculty of Science, Department of Medicinal Chemistry, Amsterdam Institute of Molecular and Life Sciences, Amsterdam, The Netherlands
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- Martine J. Smit
- Vrije Universiteit Amsterdam Faculty of Science, Department of Medicinal Chemistry, Amsterdam Institute of Molecular and Life Sciences, Amsterdam, The Netherlands
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- Git Chung
- Newcells Biotech Ltd, The Biosphere, Newcastle upon Tyne, UK
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- Majlinda Lako
- Biosciences Institute, Newcastle University, The International Centre for Life, Newcastle upon Tyne, UK
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- Lyle Armstrong
- Newcells Biotech Ltd, The Biosphere, Newcastle upon Tyne, UK
抄録
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 39 (10), 1310-1321, 2021-06-21
Oxford University Press (OUP)