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Late Breaking Abstract - Organoids and lung-on-chip to study SARS-CoV-2-mediated lung injury

Mirjam Kiener, Lea De Maddalena, Nuria Roldan, George N. Thalmann, Thomas Geiser, Nina Hobi, Marianna Kruithof-De Julio
European Respiratory Journal 2020 56: 4149; DOI: 10.1183/13993003.congress-2020.4149
Mirjam Kiener
1Urology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland
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  • For correspondence: mirjam.kiener@dbmr.unibe.ch
Lea De Maddalena
2AlveoliX AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland
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Nuria Roldan
2AlveoliX AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland
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George N. Thalmann
3Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland
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Thomas Geiser
4Department of Pneumology, Inselspital, Bern University Hospital, Bern, Switzerland
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Nina Hobi
2AlveoliX AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland
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Marianna Kruithof-De Julio
1Urology Research Laboratory, Department for BioMedical Research, University of Bern, Bern, Switzerland
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Abstract

COVID-19 is an infectious disease caused by the newly discovered coronavirus named SARS-CoV-2. The virus enters the body through the airways by exploiting the angiotensin-converting enzyme 2 (ACE2) and serine proteinase TMPRSS2. Thus, especially lung epithelial cells are attacked by the virus. In the distal lung, the virus infection leads to life-threatening alveolar damage and cytokine storm. Many excellent clinical studies described the pathology of COVID-19 progression in patients. However, impactful in vitro studies are still missing due to the exceptional difficulty to model the alveolar setting in vitro. Here, we introduce two advanced models based on organoids and lung-on-chip (LOC) technology. The models derived from primary alveolar epithelial cells were characterized by fluorescence imaging and gene expression. Barrier function and cell polarity were assessed by confocal microscopy of tight junction and transporter proteins. We showed that the LOC model and the newly developed organoids preserve alveolar type II specific markers (SP-C and HTII-280). In both models we could detect relevant amounts of ACE2 and TMPRSS2 mRNA as compared to whole lung extracts.

As a next step we will optimize the infection titer for both systems to further analyze transcriptomic changes upon SARS-CoV-2 infection. The here presented advanced in vitro models, recapitulating the distal lung, serve as complementary SARS-CoV-2 lung infection models. The LOC model will allow to simulate alveolar breakdown and cytokine storm whereas the organoid models will facilitate high-content drug screening.

  • Viruses
  • Experimental approaches
  • Epithelial cell

Footnotes

Cite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4149.

This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.

This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).

  • Copyright ©the authors 2020
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Late Breaking Abstract - Organoids and lung-on-chip to study SARS-CoV-2-mediated lung injury
Mirjam Kiener, Lea De Maddalena, Nuria Roldan, George N. Thalmann, Thomas Geiser, Nina Hobi, Marianna Kruithof-De Julio
European Respiratory Journal Sep 2020, 56 (suppl 64) 4149; DOI: 10.1183/13993003.congress-2020.4149

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Late Breaking Abstract - Organoids and lung-on-chip to study SARS-CoV-2-mediated lung injury
Mirjam Kiener, Lea De Maddalena, Nuria Roldan, George N. Thalmann, Thomas Geiser, Nina Hobi, Marianna Kruithof-De Julio
European Respiratory Journal Sep 2020, 56 (suppl 64) 4149; DOI: 10.1183/13993003.congress-2020.4149
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