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Review
. 2021 Apr 28;13(5):792.
doi: 10.3390/v13050792.

In Vitro Lung Models and Their Application to Study SARS-CoV-2 Pathogenesis and Disease

Natalie Heinen  1 , Mara Klöhn  1 , Eike Steinmann  1 , Stephanie Pfaender  1
Affiliations
Review

In Vitro Lung Models and Their Application to Study SARS-CoV-2 Pathogenesis and Disease

Natalie Heinen et al. Viruses. .

Abstract

SARS-CoV-2 has spread across the globe with an astonishing velocity and lethality that has put scientist and pharmaceutical companies worldwide on the spot to develop novel treatment options and reliable vaccination for billions of people. To combat its associated disease COVID-19 and potentially newly emerging coronaviruses, numerous pre-clinical cell culture techniques have progressively been used, which allow the study of SARS-CoV-2 pathogenesis, basic replication mechanisms, and drug efficiency in the most authentic context. Hence, this review was designed to summarize and discuss currently used in vitro and ex vivo cell culture systems and will illustrate how these systems will help us to face the challenges imposed by the current SARS-CoV-2 pandemic.

Keywords: SARS-CoV-2; air–liquid interface; cell culture; ex vivo lung; human airway epithelial cell culture; human lung organoids; in vitro lung model; lung-on-a-chip.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Organization and cellular characteristics of the human respiratory airway. Adapted from “Respiratory Epithelium”, by BioRender.com (accessed on 22 April 2021) (2021). Retrieved from https://app.biorender.com/biorender-templates (accessed on 21 April 2021).
Figure 2
Figure 2
Generation of human airway epithelial cell culture in air–liquid interface (ALI) from human airway epithelial cells (hAECs). Figure created with BioRender.com (accessed on 28 April 2021).
Figure 3
Figure 3
Development of different types of lung organoids from hiPSCs, hESCs or primary cells, with the average duration of development. Figure created with BioRender.com (accessed on 26 March 2021).
Figure 4
Figure 4
Lung-on-a-chip (A) and ex vivo (B) culture techniques. Figure was created with BioRender.com (accessed on 26 March 2021).
See this image and copyright information in PMC

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References

    1. Hsia C.C.W., Hyde D.M., Weibel E.R. Lung Structure and the Intrinsic Challenges of Gas Exchange. Compr. Physiol. 2016;6:827–895. doi: 10.1002/cphy.c150028. - DOI - PMC - PubMed
    1. Crystal R.G., Randell S.H., Engelhardt J.F., Voynow J., Sunday M.E. Airway epithelial cells: Current concepts and challenges. Proc. Am. Thorac. Soc. 2008;5:772–777. doi: 10.1513/pats.200805-041HR. - DOI - PMC - PubMed
    1. Hewitt R.J., Lloyd C.M. Regulation of immune responses by the airway epithelial cell landscape. Nat. Rev. Immunol. 2021 doi: 10.1038/s41577-020-00477-9. - DOI - PMC - PubMed
    1. Carcaterra M., Caruso C. Alveolar epithelial cell type II as main target of SARS-CoV-2 virus and COVID-19 development via NF-Kb pathway deregulation: A physio-pathological theory. Med. Hypotheses. 2021;146:110412. doi: 10.1016/j.mehy.2020.110412. - DOI - PMC - PubMed
    1. Ravindra N.G., Alfajaro M.M., Gasque V., Huston N.C., Wan H., Szigeti-Buck K., Yasumoto Y., Greaney A.M., Habet V., Chow R.D., et al. Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes. PLoS Biol. 2021;19:e3001143. doi: 10.1371/journal.pbio.3001143. - DOI - PMC - PubMed

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