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

Samantha V. Llewellyn, Ali Kermanizadeh, Victor Ude, Nicklas Raun Jacobsen, Gillian E. Conway, Ume-Kulsoom Shah, Marije Niemeijer, Martijn J. Moné, Bob Van De Water, Shambhu Roy, Wolfgang Moritz, Vicki Stone, Gareth J. S. Jenkins, Shareen H. Doak

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Article number105473
JournalToxicology in Vitro
Early online date13 Sep 2022
DOIs
Publication statusE-pub ahead of print - 13 Sep 2022

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