Transferability and reproducibility of exposed air-liquid interface co-culture lung models [* Cross-Reference *]

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Braakhuis, Hedwig M.; Gremmer, Eric R.; Bannuscher, Anne; Drasler, Barbara; Keshavan, Sandeep; Rothen-Rutishauser, Barbara; Birk, Barbara; Verlohner, Andreas; Landsiedel, Robert; Meldrum, Kirsty; Doak, Shareen H.; Clift, Martin J.D.; Erdem, Johanna Samulin; Foss, Oda A.H.; Zienolddiny-Narui, Shanbeh; Serchi, Tommaso; Moschini, Elisa; Weber, Pamina; Burla, Sabina; Kumar, Pramod; Schmid, Otmar; Zwart, Edwin; Vermeulen, Jolanda P.; Vandebriel, Rob J., 2023, "Transferability and reproducibility of exposed air-liquid interface co-culture lung models [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.EDODFD, LIST Open Repository, V1
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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 co-culture 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. (2023-07-04)
***This entry has been automatically imported via Infodoc(ASO) CSV by LIST harvest scripts. Please refer to https://doi.org/10.1016/j.impact.2023.100466 for the original and latest version of the dataset and data downloads*** (2025-09-03)
Subject Earth and Environmental Sciences
Keyword Air exposure, Air-liquid interface, Inter-laboratory comparison, Lung model, Nanomaterial, Toxicity
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