Journal article 327 views 54 downloads
Transferability and reproducibility of exposed air-liquid interface co-culture lung models
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Martin Clift ,
Johanna Samulin Erdem,
Oda A.H. Foss,
Shanbeh Zienolddiny-Narui,
Tommaso Serchi,
Elisa Moschini,
Pamina Weber,
Sabina Burla,
Pramod Kumar,
Otmar Schmid,
Edwin Zwart,
Jolanda P. Vermeulen,
Rob J. Vandebriel
NanoImpact, Volume: 31, Start page: 100466
Swansea University Authors:
Kirsty Meldrum, Shareen Doak , Martin Clift
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© 2023 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/)
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DOI (Published version): 10.1016/j.impact.2023.100466
Abstract
Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI)...
| Published in: | NanoImpact |
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| ISSN: | 2452-0748 |
| Published: |
Elsevier BV
2023
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| Online Access: |
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa63446 |
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| Abstract: |
Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a coculture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes).The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels.Results: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO2) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels.The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production.Conclusion: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline. |
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| Keywords: |
Inter-laboratory comparison, lung model, air-liquid exposure, nanomaterial, toxicity |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
EU H2020: Project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment), No. 760813 |
| Start Page: |
100466 |