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Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids

Samantha Llewellyn, Ali Kermanizadeh, Victor Ude, Nicklas Raun Jacobsen, Gill Conway Orcid Logo, Ume-kulsoom Shah Orcid Logo, Marije Niemeijer, Martijn J. Moné, Bob van de Water, Shambhu Roy, Wolfgang Moritz, Vicki Stone, Gareth Jenkins Orcid Logo, Shareen Doak Orcid Logo

Toxicology in Vitro, Volume: 85, Start page: 105473

Swansea University Authors: Samantha Llewellyn, Gill Conway Orcid Logo, Ume-kulsoom Shah Orcid Logo, Gareth Jenkins Orcid Logo, Shareen Doak Orcid Logo

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DOI (Published version): 10.1016/j.tiv.2022.105473

Abstract

To reduce, replace, and refine in vivo testing, there is increasing emphasis on the development of more physiologically relevant in vitro test systems to improve the reliability of non-animal-based methods for hazard assessment. When developing new approach methodologies, it is important to standard...

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Published in: Toxicology in Vitro
ISSN: 0887-2333
Published: Elsevier BV 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa61191
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spelling 2022-10-06T13:56:10.3832545 v2 61191 2022-09-13 Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids fb4b6c686b654c6687c4063974b5cc8c Samantha Llewellyn Samantha Llewellyn true false e33e0ee5a076ad91fe6615117caa1800 0000-0002-5991-0960 Gill Conway Gill Conway true false bcef4e069220a4b85f8a2c0cc3059487 0000-0002-0594-580X Ume-kulsoom Shah Ume-kulsoom Shah true false a44095d26187304e903da7ca778697b6 0000-0002-5437-8389 Gareth Jenkins Gareth Jenkins true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false 2022-09-13 BMS To reduce, replace, and refine in vivo testing, there is increasing emphasis on the development of more physiologically relevant in vitro test systems to improve the reliability of non-animal-based methods for hazard assessment. When developing new approach methodologies, it is important to standardize the protocols and demonstrate the methods can be reproduced by multiple laboratories. The aim of this study was to assess the transferability and reproducibility of two advanced in vitro liver models, the Primary Human multicellular microtissue liver model (PHH) and the 3D HepG2 Spheroid Model, for nanomaterial (NM) and chemical hazard assessment purposes. The PHH model inter-laboratory trial showed strong consistency across the testing sites. All laboratories evaluated cytokine release and cytotoxicity following exposure to titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles. No significant difference was observed in cytotoxicity or IL-8 release for the test materials. The data were reproducible with all three laboratories with control readouts within a similar range. The PHH model ZnO induced the greatest cytotoxicity response at 50.0 μg/mL and a dose-dependent increase in IL-8 release. For the 3D HepG2 spheroid model, all test sites were able to construct the model and demonstrated good concordance in IL-8 cytokine release and genotoxicity data. This trial demonstrates the successful transfer of new approach methodologies across multiple laboratories, with good reproducibility for several hazard endpoints. Journal Article Toxicology in Vitro 85 105473 Elsevier BV 0887-2333 Inter-laboratory trial; 3D liver models; Hepatotoxicity; Nanotoxicology; Genotoxicity 1 12 2022 2022-12-01 10.1016/j.tiv.2022.105473 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University SU Library paid the OA fee (TA Institutional Deal) This research was funded by European Union's Horizon 2020 research and innovation program for the PATROLS project, under grant agreement No.760813. 2022-10-06T13:56:10.3832545 2022-09-13T09:38:47.7071367 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Samantha Llewellyn 1 Ali Kermanizadeh 2 Victor Ude 3 Nicklas Raun Jacobsen 4 Gill Conway 0000-0002-5991-0960 5 Ume-kulsoom Shah 0000-0002-0594-580X 6 Marije Niemeijer 7 Martijn J. Moné 8 Bob van de Water 9 Shambhu Roy 10 Wolfgang Moritz 11 Vicki Stone 12 Gareth Jenkins 0000-0002-5437-8389 13 Shareen Doak 0000-0002-6753-1987 14 61191__25328__0ecddedbe0554f88935dc3f5684bde88.pdf 61191_VoR.pdf 2022-10-06T13:53:59.9544677 Output 1194912 application/pdf Version of Record true © 2022 The Authors. This is an open access article under the CC BY license true eng http://creativecommons.org/licenses/by/4.0/
title Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
spellingShingle Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
Samantha Llewellyn
Gill Conway
Ume-kulsoom Shah
Gareth Jenkins
Shareen Doak
title_short Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
title_full Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
title_fullStr Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
title_full_unstemmed Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
title_sort Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids
author_id_str_mv fb4b6c686b654c6687c4063974b5cc8c
e33e0ee5a076ad91fe6615117caa1800
bcef4e069220a4b85f8a2c0cc3059487
a44095d26187304e903da7ca778697b6
8f70286908f67238a527a98cbf66d387
author_id_fullname_str_mv fb4b6c686b654c6687c4063974b5cc8c_***_Samantha Llewellyn
e33e0ee5a076ad91fe6615117caa1800_***_Gill Conway
bcef4e069220a4b85f8a2c0cc3059487_***_Ume-kulsoom Shah
a44095d26187304e903da7ca778697b6_***_Gareth Jenkins
8f70286908f67238a527a98cbf66d387_***_Shareen Doak
author Samantha Llewellyn
Gill Conway
Ume-kulsoom Shah
Gareth Jenkins
Shareen Doak
author2 Samantha Llewellyn
Ali Kermanizadeh
Victor Ude
Nicklas Raun Jacobsen
Gill Conway
Ume-kulsoom Shah
Marije Niemeijer
Martijn J. Moné
Bob van de Water
Shambhu Roy
Wolfgang Moritz
Vicki Stone
Gareth Jenkins
Shareen Doak
format Journal article
container_title Toxicology in Vitro
container_volume 85
container_start_page 105473
publishDate 2022
institution Swansea University
issn 0887-2333
doi_str_mv 10.1016/j.tiv.2022.105473
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
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
document_store_str 1
active_str 0
description To reduce, replace, and refine in vivo testing, there is increasing emphasis on the development of more physiologically relevant in vitro test systems to improve the reliability of non-animal-based methods for hazard assessment. When developing new approach methodologies, it is important to standardize the protocols and demonstrate the methods can be reproduced by multiple laboratories. The aim of this study was to assess the transferability and reproducibility of two advanced in vitro liver models, the Primary Human multicellular microtissue liver model (PHH) and the 3D HepG2 Spheroid Model, for nanomaterial (NM) and chemical hazard assessment purposes. The PHH model inter-laboratory trial showed strong consistency across the testing sites. All laboratories evaluated cytokine release and cytotoxicity following exposure to titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles. No significant difference was observed in cytotoxicity or IL-8 release for the test materials. The data were reproducible with all three laboratories with control readouts within a similar range. The PHH model ZnO induced the greatest cytotoxicity response at 50.0 μg/mL and a dose-dependent increase in IL-8 release. For the 3D HepG2 spheroid model, all test sites were able to construct the model and demonstrated good concordance in IL-8 cytokine release and genotoxicity data. This trial demonstrates the successful transfer of new approach methodologies across multiple laboratories, with good reproducibility for several hazard endpoints.
published_date 2022-12-01T04:19:51Z
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