Evidence map›Paper›PMID 34667862›Full record

ArticleLaryngoscope investigative otolaryngology2021

Development of a physiological model of human middle ear epithelium.

Michael William Mather, Bernard Verdon, Rachel Anne Botting, Justin Engelbert, Livia Delpiano, Xin Xu, Catherine Hatton, Tracey Davey, Steven Lisgo, Philip Yates and 5 more

Open access · goldAbstract read
In one paragraph

Article in Laryngoscope investigative otolaryngology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Measuring the Possibility of Middle Ear Discharge for COVID-19 Test Material.Interdisciplinary perspectives on infectious diseases · 2022
    Review
  3. Article
  4. Development of a physiological model of human middle ear epithelium.Laryngoscope investigative otolaryngology · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 3 institutions in 1 country.

Michael William MatherFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.ORCID https://orcid.org/0000-0001-7972-7111
Bernard VerdonFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Rachel Anne BottingFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Justin EngelbertFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Livia DelpianoFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Xin XuNewcastle Biobank, Faculty of Medical Sciences Newcastle University Newcastle-upon-Tyne UK.
Catherine HattonFaculty of Medical Sciences Translational and Clinical Research Institute, Newcastle University Newcastle-upon-Tyne UK.
Tracey DaveyElectron Microscopy Research Services, Faculty of Medical Sciences Newcastle University Newcastle-upon-Tyne UK.
Steven LisgoFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Philip YatesDepartment of Otolaryngology Freeman Hospital Newcastle-upon-Tyne UK.
Nicholas DaweDepartment of Otolaryngology Freeman Hospital Newcastle-upon-Tyne UK.
Colin D BingleDepartment of Infection, Immunity and Cardiovascular Disease The Medical School Sheffield UK.
Muzlifah HaniffaFaculty of Medical Sciences Biosciences Institute, Newcastle University Newcastle-upon-Tyne UK.
Jason PowellDepartment of Otolaryngology Freeman Hospital Newcastle-upon-Tyne UK.
Chris WardFaculty of Medical Sciences Translational and Clinical Research Institute, Newcastle University Newcastle-upon-Tyne UK.
Newcastle University · GBFreeman Hospital · GBUniversity of Sheffield · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

introductionOtitis 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.

methodsWe 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.

resultsWe 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.

conclusionWe 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.

Indexed as

biological modelsotitis mediaotorhinolaryngologic diseasesrespiratory mucosaSARS‐CoV‐2

Identifiers

PMID34667862
PMCPMC8513425
OpenAlexW3200753890

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.