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

Journal article


Llewellyn, S. V., Kermanizadeh, A., Ude, V., Jacobsen, N. R., Conway, G. E., Shah, U. K., Niemeijer, M., van de Water, B., Roy, S., Moritz, W., Stone, V., Jenkins, G. J. S. and Doak, S. H. 2022. Assessing the transferability and reproducibility of 3D in vitro liver models from primary human multi-cellular microtissues to cell-line based HepG2 spheroids. Toxicology in vitro. 85 (105473), pp. 1-9. https://doi.org/10.1016/j.tiv.2022.105473
AuthorsLlewellyn, S. V., Kermanizadeh, A., Ude, V., Jacobsen, N. R., Conway, G. E., Shah, U. K., Niemeijer, M., van de Water, B., Roy, S., Moritz, W., Stone, V., Jenkins, G. J. S. and Doak, S. H.
Abstract

To reduce, replace, and refine in vivo testing, there is increasing emphasis on the development of more physilologically 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.

KeywordsInter-laboratory trial; 3D liver models; Hepatotoxicity; Nanotoxicology; Genotoxicity
Year2022
JournalToxicology in vitro
Journal citation85 (105473), pp. 1-9
PublisherElsevier
ISSN0887-2333
Digital Object Identifier (DOI)https://doi.org/10.1016/j.tiv.2022.105473
Web address (URL)https://www.sciencedirect.com/science/article/pii/S0887233322001710?via%3Dihub
Accepted author manuscript
File Access Level
Open
Publisher's version
File Access Level
Open
Output statusPublished
Publication dates
Online13 Sep 2022
Publication process dates
Accepted08 Sep 2022
Deposited02 Nov 2022
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