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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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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
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa61191
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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 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.
Keywords: Inter-laboratory trial; 3D liver models; Hepatotoxicity; Nanotoxicology; Genotoxicity
College: Faculty of Medicine, Health and Life Sciences
Funders: This research was funded by European Union's Horizon 2020 research and innovation program for the PATROLS project, under grant agreement No.760813.
Start Page: 105473