Cellular Effects in an<i>In Vitro</i>Human 3D Cellular Airway Model and A549/BEAS-2B<i>In Vitro</i>Cell Cultures Following Air Exposure to Cerium Oxide Particles at an Air–Liquid Interface

Kooter, Ingeborg M.; Gröllers-Mulderij, Mariska; Steenhof, Maaike; Duistermaat, Evert; Acker, F.A.A. van; Staal, Yvonne C.M.; Tromp, Peter; Schoen, Eric D.; Kuiper, C.F.; Someren, Eugene P. van

doi:10.1089/aivt.2015.0030

Cited by 25 publications

(30 citation statements)

References 24 publications

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“…It was only when the complexity of differentiated 3D cells were added that studies start to diverge. Kooter et al, 2 who analyzed the delivery of aerosolized cerium oxide (CeO 2 ) in 2D A549, BEAS-2B cell monolayers, and 3D MucilAir cell cultures, observed a similar trend. The A459 and BEAS-2B cells responded to exposures in the range of 0.04-3.0 lg/cm 2 (primary particle sizes 0.75 lm to 13.8 nm) and demonstrated cytotoxicity (lactate dehydrogenase release), pro-inflammatory cytokine responses (interleukin 8 release), and genotoxicity.…”

Section: Discussionmentioning

confidence: 71%

“…Consistently no response was seen in either EpiAirway or MucilAir (Studies 3, 4, and 5) at corresponding doses. Kooter et al, 2 postulated that the lack of observed response in MucilAir was due to the protective physiology of the 3D structure compared with the simpler 2D monolayers. The results from this case study confirm this observation that the 3D cultures require a significantly higher dose to achieve a response.…”

Section: Discussionmentioning

confidence: 99%

“…T he development of whole aerosol (whole smoke) exposure systems has been driven by the necessity to develop techniques to deliver aerosols in vitro in ways that mimic human exposure to cigarette smoke and other inhaled chemicals with increasingly physiological accuracy. [1][2][3] Cigarette smoke is a complex dynamic aerosol consisting of thousands of chemicals distributed in the particulate and vapor phases, with some transitioning between both phases. 4 Due to the complex nature of cigarette smoke, appropriate analysis and exposure is a challenging multifactorial problem.…”

Section: Introductionmentioning

confidence: 99%

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A Case Study for the Comparison ofIn VitroData Across Multiple Aerosol Exposure Studies with Extrapolation to Human Dose

Thorne

Bishop

Haswell

et al. 2018

Applied In Vitro Toxicology

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In vitro aerosol systems offer advantages in generating aerosols and exposing cell cultures at the air-liquid interface (ALI), mimicking human exposure. However, dilution technologies, principles, and characteristics of exposure chambers differ between systems. In addition, various cell types and biological end points can be assessed, meaning that in vitro aerosol data are presented in different ways, so researchers are unable to compare data between systems, studies, and laboratories. In this case study we present the comparison of in vitro data across multiple aerosol exposure studies using a 3R4F reference tobacco product. The first aim assessed whether a consistent in vitro dosimetry approach could gain insight into the characterization of ALI aerosol exposure systems. The second aim assessed whether cytotoxicity data sets generated on contrasting exposure systems with different experimental setups could be directly compared. Cytotoxicity data generated from five independent studies were compared. When plotted on the x-axis as a function of dilution principle, the ''standard way'' to present whole aerosol data, there was little read across between the data sets. Expressing each data set as a function of particulate dose (lg/cm 2) and nicotine concentration (mg), however, allowed comparisons between all data sets and with human daily exposure estimates. Furthermore, compared as a function of dose, the data set showed remarkable commonalities between themselves despite clear study differences. The data demonstrate that in vitro dosimetry techniques can align data between contrasting setups and experimental protocols to facilitate comparisons and provide a link between in vitro, in vivo, and human dosimetry studies.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Case Study for the Comparison ofIn VitroData Across Multiple Aerosol Exposure Studies with Extrapolation to Human Dose

Thorne

Bishop

Haswell

et al. 2018

Applied In Vitro Toxicology

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“…It harbours a variety of physiologically relevant cellular mechanisms, such as an intact mucociliary system and cytokine secretory properties upon lipopolysaccharide (LPS) stimulation, and, thus, resembles the in vivo situation as close as possible. Previous studies from our research group already demonstrated its superiority over the use of lung epithelial cell lines and showed its utility in the evaluation of respiratory absorption and toxicity assessment of NPs (Kooter et al, ; Kuper et al, ; Reus et al, ; Zarcone et al, ).…”

Section: Introductionmentioning

confidence: 97%

A practical approach to assess inhalation toxicity of metal oxide nanoparticles in vitro

Dankers

Kuper

Boumeester

et al. 2017

J of Applied Toxicology

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Exposure of humans to metal oxide nanoparticles (NPs) occurs mainly via air, and inhaled metal oxide NPs may generate inflammation. The aim of this study was to investigate the proinflammatory potential of six metal oxide NPs (CeO , Mn O , CuO, ZnO, Co O and WO ; 27-108 μg ml ) using human primary 3-dimensional airway epithelium (MucilAir™) and dendritic cell (DC) models. Metal oxide NPs were mainly aggregated/agglomerated in the cell media, as determined by dynamic light scattering, scanning electron microscopy and differential centrifugal sedimentation. WO and ZnO were highly soluble, both with and without respiratory mucus. Proinflammatory signalling by the epithelium was evaluated after a 24 hour exposure by increased interleukin-6 and -8 and monocyte chemoattractant protein 1 cytokine release, which occurred only for CuO. Moreover, maturation of immature human DCs, which play a key role in the lung immune system, were evaluated by expression of surface markers HLA-DR, CD80, CD83 and CD86 after a 48 hour exposure. Only Mn O consistently upregulated DC maturation markers. Furthermore, by addition of medium from metal oxide NP-exposed 3-dimensional airway cultures to metal oxide NP-exposed DC cultures, the interplay between lung epithelium and DCs was studied. Such an interplay was again only observed for Mn O and in one of five DC donors. Our results show that, even when using dosages that represent very high in vivo exposure levels, up to 27 hours of constant human airway exposure, metal oxide NPs cause minimal proinflammatory effects and that epithelial cells not necessarily interfere with DC maturation upon metal oxide NP exposure. The present approach exemplifies a relevant translation towards human safety assessment.

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“…[3] Cell lines have been widely used for nanotoxicological testing and although they are easy and cheap to handle, these models have disadvantages such as being immortalized, having reduced differentiation ability and lack of individual variety, calling into question how adequately they represent cell behavior in vivo. [4] Primary cells are a better choice to reflect the actual cell behavior, but they in turn have limited life span, and similarly to cell lines, consist of only one cell type. [5] To overcome these shortcomings, advanced 3D in vitro systems consisting of polarized mucociliary differentiated airway epithelial cell layers, that more resembles the human airway epithelium (MucilAir), have been developed.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non‐Animal Methods for Hazard Assessment

Ndika

Ilves

Kooter

et al. 2020

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The diversity and increasing prevalence of products derived from engineered nanomaterials (ENM), warrants implementation of non‐animal approaches to health hazard assessment for ethical and practical reasons. Although non‐animal approaches are becoming increasingly popular, there are almost no studies of side‐by‐side comparisons with traditional in vivo assays. Here, transcriptomics is used to investigate mechanistic similarities between healthy/asthmatic models of 3D air–liquid interface (ALI) cultures of donor‐derived human bronchial epithelia cells, and mouse lung tissue, following exposure to copper oxide ENM. Only 19% of mouse lung genes with human orthologues are not expressed in the human 3D ALI model. Despite differences in taxonomy and cellular complexity between the systems, a core subset of matching genes cluster mouse and human samples strictly based on ENM dose (exposure severity). Overlapping gene orthologue pairs are highly enriched for innate immune functions, suggesting an important and maybe underestimated role of epithelial cells. In conclusion, 3D ALI models based on epithelial cells, are primed to bridge the gap between traditional 2D in vitro assays and animal models of airway exposure, and transcriptomics appears to be a unifying dose metric that links in vivo and in vitro test systems.

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Cellular Effects in anIn VitroHuman 3D Cellular Airway Model and A549/BEAS-2BIn VitroCell Cultures Following Air Exposure to Cerium Oxide Particles at an Air–Liquid Interface

Cited by 25 publications

References 24 publications

A Case Study for the Comparison ofIn VitroData Across Multiple Aerosol Exposure Studies with Extrapolation to Human Dose

A Case Study for the Comparison ofIn VitroData Across Multiple Aerosol Exposure Studies with Extrapolation to Human Dose

A practical approach to assess inhalation toxicity of metal oxide nanoparticles in vitro

Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non‐Animal Methods for Hazard Assessment

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