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Development of a physiological model of human middle ear epithelium

Lookup NU author(s): Dr Michael Mather, Dr Bernard Verdon, Dr Rachel Botting, Justin Engelbert, Livia Delpiano, Xin Xu, Tracey Davey, Dr Steven Lisgo, Philip Yates, Nick Dawe, Professor Muzlifah Haniffa, Jason Powell, Professor Christopher Ward

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2021 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society. Introduction: Otitis media is an umbrella term for middle ear inflammation; ranging from acute infection to chronic mucosal disease. It is a leading cause of antimicrobial therapy prescriptions and surgery in children. Despite this, treatments have changed little in over 50 years. Research has been limited by the lack of physiological models of middle ear epithelium. Methods: We develop a novel human middle ear epithelial culture using an air-liquid interface (ALI) system; akin to the healthy ventilated middle ear in vivo. We validate this using immunohistochemistry, immunofluorescence, scanning and transmission electron microscopy, and membrane conductance studies. We also utilize this model to perform a pilot challenge of middle ear epithelial cells with SARS-CoV-2. Results: We demonstrate that human middle ear epithelial cells cultured at an ALI undergo mucociliary differentiation to produce diverse epithelial subtypes including basal (p63+), goblet (MUC5AC+, MUC5B+), and ciliated (FOXJ1+) cells. Mature ciliagenesis is visualized and tight junction formation is shown with electron microscopy, and confirmed by membrane conductance. Together, these demonstrate this model reflects the complex epithelial cell types which exist in vivo. Following SARS-CoV-2 challenge, human middle ear epithelium shows positive viral uptake, as measured by polymerase chain reaction and immunohistochemistry. Conclusion: We describe a novel physiological system to study the human middle ear. This can be utilized for translational research into middle ear diseases. We also demonstrate, for the first time under controlled conditions, that human middle ear epithelium is susceptible to SARS-CoV-2 infection, which has important clinical implications for safe otological surgery. Level of Evidence: NA.


Publication metadata

Author(s): Mather MW, Verdon B, Botting RA, Engelbert J, Delpiano L, Xu X, Hatton C, Davey T, Lisgo S, Yates P, Dawe N, Bingle CD, Haniffa M, Powell J, Ward C

Publication type: Article

Publication status: Published

Journal: Laryngoscope Investigative Otolaryngology

Year: 2021

Pages: Epub ahead of print

Online publication date: 18/09/2021

Acceptance date: 09/09/2021

Date deposited: 02/10/2021

ISSN (electronic): 2378-8038

Publisher: John Wiley and Sons Inc.

URL: https://doi.org/10.1002/lio2.661

DOI: 10.1002/lio2.661


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