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Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier

Sarah M. Mitchell, Kirsty Meldrum, Josh Bateman, Teresa D. Tetley, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

In vitro models, Volume: 3, Issue: 2-3, Pages: 125 - 137

Swansea University Authors: Kirsty Meldrum, Josh Bateman, Shareen Doak Orcid Logo, Martin Clift Orcid Logo

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DOI (Published version): 10.1007/s44164-024-00075-2

Abstract

Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution a...

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Published in: In vitro models
ISSN: 2731-3441
Published: Springer Science and Business Media LLC 2024
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URI: https://cronfa.swan.ac.uk/Record/cronfa67177
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spelling 2024-08-29T16:33:44.3291226 v2 67177 2024-07-25 Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier bbb7bd27bfa3c6ffc73da8facfebc793 Kirsty Meldrum Kirsty Meldrum true false 9046b92fe972861a67aec6be5e093c00 Josh Bateman Josh Bateman true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false 71bf49b157691e541950f5c3f49c9169 0000-0001-6133-3368 Martin Clift Martin Clift true false 2024-07-25 MEDS Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings. Here, an in vitro model of the alveolar barrier has been created in preparation for use in the quasi-air liquid interface (qALI) and (aerosol) air–liquid interface (ALI) exposures. The model consists of an alveolar type 1-like cell line (TT1), an alveolar type 2-like cell line (NCI-H441) and a model of (alveolar) macrophages (dTHP-1). The model formulates a complex, multi-cellular system, cultured at the air–liquid interface, that mimics the apical layer of the alveolar epithelial region in the human lung. Characterisation data has shown that both TT1 and NCI-H441 epithelial cells are able to be cultured together in addition to dTHP-1 cells through imaging (morphology), pro-inflammatory response and viability measurements. This dataset also demonstrates evidence of a reasonable barrier created by the cell culture in comparison to negative controls. Furthermore, it shows that while maintaining a low baseline of (pro)-inflammatory mediator expression during normal conditions, the model is highly responsive to inflammatory stimuli. This model is proposed to be suitable for use in toxicology testing of inhaled exogenous agents. Journal Article In vitro models 3 2-3 125 137 Springer Science and Business Media LLC 2731-3441 In vitro; Multi-cellular system; Epithelial cells; New approach Methodologies (NAMs); Alveolar; 3D cell culture 1 6 2024 2024-06-01 10.1007/s44164-024-00075-2 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University SU Library paid the OA fee (TA Institutional Deal) This work has been funded by a combination of scholarships awarded by Knowledge Economy Skills Scholarships (KESS) 2 and UKHSA (UK Health Security Agency). 2024-08-29T16:33:44.3291226 2024-07-25T10:26:57.4294359 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Sarah M. Mitchell 1 Kirsty Meldrum 2 Josh Bateman 3 Teresa D. Tetley 4 Shareen Doak 0000-0002-6753-1987 5 Martin Clift 0000-0001-6133-3368 6 67177__31178__1aeda1a7cf474ddba17068077139e282.pdf 67177.VoR.pdf 2024-08-29T16:31:40.7561472 Output 1658973 application/pdf Version of Record true © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License. true eng http://creativecommons.org/licenses/by/4.0/
title Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
spellingShingle Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
Kirsty Meldrum
Josh Bateman
Shareen Doak
Martin Clift
title_short Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
title_full Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
title_fullStr Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
title_full_unstemmed Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
title_sort Development and characterisation of a novel complex triple cell culture model of the human alveolar epithelial barrier
author_id_str_mv bbb7bd27bfa3c6ffc73da8facfebc793
9046b92fe972861a67aec6be5e093c00
8f70286908f67238a527a98cbf66d387
71bf49b157691e541950f5c3f49c9169
author_id_fullname_str_mv bbb7bd27bfa3c6ffc73da8facfebc793_***_Kirsty Meldrum
9046b92fe972861a67aec6be5e093c00_***_Josh Bateman
8f70286908f67238a527a98cbf66d387_***_Shareen Doak
71bf49b157691e541950f5c3f49c9169_***_Martin Clift
author Kirsty Meldrum
Josh Bateman
Shareen Doak
Martin Clift
author2 Sarah M. Mitchell
Kirsty Meldrum
Josh Bateman
Teresa D. Tetley
Shareen Doak
Martin Clift
format Journal article
container_title In vitro models
container_volume 3
container_issue 2-3
container_start_page 125
publishDate 2024
institution Swansea University
issn 2731-3441
doi_str_mv 10.1007/s44164-024-00075-2
publisher Springer Science and Business Media LLC
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Owing to increased pressure from ethical groups and the public to avoid unnecessary animal testing, the need for new, responsive and biologically relevant in vitro models has surged. Models of the human alveolar epithelium are of particular interest since thorough investigations into air pollution and the effects of inhaled nanoparticles and e-cigarettes are needed. The lung is a crucial organ of interest due to potential exposures to endogenous material during occupational and ambient settings. Here, an in vitro model of the alveolar barrier has been created in preparation for use in the quasi-air liquid interface (qALI) and (aerosol) air–liquid interface (ALI) exposures. The model consists of an alveolar type 1-like cell line (TT1), an alveolar type 2-like cell line (NCI-H441) and a model of (alveolar) macrophages (dTHP-1). The model formulates a complex, multi-cellular system, cultured at the air–liquid interface, that mimics the apical layer of the alveolar epithelial region in the human lung. Characterisation data has shown that both TT1 and NCI-H441 epithelial cells are able to be cultured together in addition to dTHP-1 cells through imaging (morphology), pro-inflammatory response and viability measurements. This dataset also demonstrates evidence of a reasonable barrier created by the cell culture in comparison to negative controls. Furthermore, it shows that while maintaining a low baseline of (pro)-inflammatory mediator expression during normal conditions, the model is highly responsive to inflammatory stimuli. This model is proposed to be suitable for use in toxicology testing of inhaled exogenous agents.
published_date 2024-06-01T20:46:01Z
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