Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs
Abstract Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air–Liquid Interface (ALI) models, yet the limited...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11700-z |
| _version_ | 1811253227854757888 |
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| author | Georgios Stroulios Tyler Brown Giulia Moreni Douglas Kondro Alessandro Dei Allen Eaves Sharon Louis Juan Hou Wing Chang Dasja Pajkrt Katja C. Wolthers Adithya Sridhar Salvatore Simmini |
| author_facet | Georgios Stroulios Tyler Brown Giulia Moreni Douglas Kondro Alessandro Dei Allen Eaves Sharon Louis Juan Hou Wing Chang Dasja Pajkrt Katja C. Wolthers Adithya Sridhar Salvatore Simmini |
| author_sort | Georgios Stroulios |
| collection | DOAJ |
| description | Abstract Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air–Liquid Interface (ALI) models, yet the limited accessibility of the organoids’ apical side has hindered their applications in studies focusing on host–pathogen interactions. Here, we describe a scalable, fast and efficient way to generate airway organoids with the apical side externally exposed. These apical-out airway organoids are generated in an Extracellular Matrix (ECM)-free environment from 2D-expanded bronchial epithelial cells and differentiated in suspension to develop uniformly-sized organoid cultures with robust ciliogenesis. Differentiated apical-out airway organoids are susceptible to infection with common respiratory viruses and show varying responses upon treatment with antivirals. In addition to the ease of apical accessibility, these apical-out airway organoids offer an alternative in vitro model to study host–pathogen interactions in higher throughput than the traditional air–liquid interface model. |
| first_indexed | 2024-04-12T16:46:43Z |
| format | Article |
| id | doaj.art-0d5f0d05c1cd42b89ea970cb80e10112 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-12T16:46:43Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-0d5f0d05c1cd42b89ea970cb80e101122022-12-22T03:24:32ZengNature PortfolioScientific Reports2045-23222022-05-0112111410.1038/s41598-022-11700-zApical-out airway organoids as a platform for studying viral infections and screening for antiviral drugsGeorgios Stroulios0Tyler Brown1Giulia Moreni2Douglas Kondro3Alessandro Dei4Allen Eaves5Sharon Louis6Juan Hou7Wing Chang8Dasja Pajkrt9Katja C. Wolthers10Adithya Sridhar11Salvatore Simmini12STEMCELL Technologies UK Ltd.STEMCELL Technologies Inc.Department of Medical Microbiology, OrganoVIR Labs, Amsterdam UMC Location University of AmsterdamSTEMCELL Technologies UK Ltd.STEMCELL Technologies UK Ltd.STEMCELL Technologies UK Ltd.STEMCELL Technologies Inc.STEMCELL Technologies China Co. Ltd.STEMCELL Technologies UK Ltd.Department of Pediatric Infectious Diseases, Emma Children’s Hospital, Amsterdam UMC Location University of AmsterdamDepartment of Medical Microbiology, OrganoVIR Labs, Amsterdam UMC Location University of AmsterdamDepartment of Medical Microbiology, OrganoVIR Labs, Amsterdam UMC Location University of AmsterdamSTEMCELL Technologies UK Ltd.Abstract Airway organoids are polarized 3D epithelial structures that recapitulate the organization and many of the key functions of the in vivo tissue. They present an attractive model that can overcome some of the limitations of traditional 2D and Air–Liquid Interface (ALI) models, yet the limited accessibility of the organoids’ apical side has hindered their applications in studies focusing on host–pathogen interactions. Here, we describe a scalable, fast and efficient way to generate airway organoids with the apical side externally exposed. These apical-out airway organoids are generated in an Extracellular Matrix (ECM)-free environment from 2D-expanded bronchial epithelial cells and differentiated in suspension to develop uniformly-sized organoid cultures with robust ciliogenesis. Differentiated apical-out airway organoids are susceptible to infection with common respiratory viruses and show varying responses upon treatment with antivirals. In addition to the ease of apical accessibility, these apical-out airway organoids offer an alternative in vitro model to study host–pathogen interactions in higher throughput than the traditional air–liquid interface model.https://doi.org/10.1038/s41598-022-11700-z |
| spellingShingle | Georgios Stroulios Tyler Brown Giulia Moreni Douglas Kondro Alessandro Dei Allen Eaves Sharon Louis Juan Hou Wing Chang Dasja Pajkrt Katja C. Wolthers Adithya Sridhar Salvatore Simmini Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs Scientific Reports |
| title | Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| title_full | Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| title_fullStr | Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| title_full_unstemmed | Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| title_short | Apical-out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| title_sort | apical out airway organoids as a platform for studying viral infections and screening for antiviral drugs |
| url | https://doi.org/10.1038/s41598-022-11700-z |
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