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Transferability and reproducibility of exposed air-liquid interface co-culture lung models.
NanoImpact 31:100466 (2023)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Air Exposure ; Air-liquid Interface ; Inter-laboratory Comparison ; Lung Model ; Nanomaterial ; Toxicity; In-vitro Cytotoxicity; Nano-titanium Dioxide; Pulmonary Inflammation; Inhalation Exposure; Particles; Toxicity; Cells; Tio2; Nanoparticles; Rats
ISSN (print) / ISBN
2452-0748
e-ISSN
2452-0748
Zeitschrift
NanoImpact
Quellenangaben
Band: 31,
Artikelnummer: 100466
Verlag
Elsevier
Verlagsort
Amsterdam
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Lung Health and Immunity (LHI)
Förderungen
Dutch Ministry of Infrastructure and Water Management
EU
European Union
National Institute of Occupational Health, Oslo, Norway
EU-project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment)
EU
European Union
National Institute of Occupational Health, Oslo, Norway
EU-project PATROLS (Physiologically Anchored Tools for Realistic nanomaterial hazard aSsessment)