Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

Neilson, Louise; Mankus, Courtney; Thorne, David; Jackson, George R.; DeBay, Jason; Meredith, Clive

doi:10.1016/j.tiv.2015.05.018

Cited by 124 publications

(120 citation statements)

References 52 publications

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“…Whilst not as physiologically relevant as work involving models at the air-liquid-interface (ALI) such as the study by Neilson et al (2015), the methodology used has allowed us to test a large range of brands and flavours; fifteen in total, at four concentrations, across four cell lines, performed in quadruplicate. A number of these tests were then repeated using the additional cell lines; THP-1, Wi38 and CALU-3.…”

Section: Discussionmentioning

confidence: 99%

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

Leslie

Bathrinarayanan

Jackson

et al. 2017

Inhalation Toxicology

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Kingdom. E-mail addresses; l.j.leslie@aston.ac.uk; vasanthp@aston.ac.uk; jacksop1@aston.ac.uk; mabialaa@aston.ac.uk; pallettr@aston.ac.uk; stillmac@aston.ac.uk; l.marshall@aston.ac.uk A comparative study of electronic cigarette vapour extracts on airwayrelated cell lines in vitroThe use of electronic cigarettes (ECs) is rapidly increasing worldwide, however scientific evidence regarding EC cytotoxicity is limited. The aim of this study was to evaluate the acute cytotoxicity of EC vapour extract (ECE) on airway-related cells in vitro.Cigarette smoke extract (CSE), vapour extract of fifteen brands/flavours of ECs and the extract from the E-vehicle (propylene glycol and glycerine) was collected. Extracts, in concentrations of 100% to 12.5%, were added to human bronchial epithelial (BEAS-2B, IB3-1 and C38), fibroblast (Wi-38) and macrophage (J774 and THP-1) cell lines.Viability was assessed after 24 hours using a standard XTT assay. Viability of less than 70% of control (no extract) was considered cytotoxic according to UNI EN ISO 10993-5 standards.CSE displayed a concentration-dependent influence on cell viability across all four cell lines with 100% producing the most toxic effect, therefore validating the model. ECEs reduced viability although this was not correlated with nicotine content or the Evehicle. However, several flavours proved cytotoxic, with variation between different brands and cell lines.These data indicate that not all ECs are the same and that use of a particular flavour or brand may have differing effects. The cell line used is also an important factor. More research is crucial to ascertain the health effects of different ECs before they can be accepted as a safe alternative to tobacco cigarettes.Keywords: Electronic cigarettes; airways; cytotoxicity; epithelials; in vitro models 3 IntroductionElectronic cigarettes (EC) first emerged onto the market in China in 2004 and entered the US market in 2007 (Regan et al. 2013). Advertised as a safe alternative to traditional tobacco cigarettes, EC were soon introduced across different countries and their market has steadily risen. According to the UK's public health charity, Action on Smoking and Health (ASH), 2.6 million adults in Great Britain currently use EC (ASH 2015). There has been a rapid global progression amongst high and low income countries, with EC use stabilising at around 17% of adult smokers, although awareness of these products is much higher, according to data pulled together in a recent Public Health England report (Britton and Bogdanovica 2014).The body of research performed on the acute and chronic effects of ECs on human health is limited (Breland et al. 2014). There are a number of challenges associated with EC research. The lack of a standardised testing protocol to evaluate different products means that there is no consensus between academic researchers, manufacturers and stake-holders (Orr 2014). Proper toxicological evaluations of ECs by the regulatory bodies are also lacking.The liquid component of EC, known as E-liq...

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Section: Discussionmentioning

confidence: 99%

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

Leslie

Bathrinarayanan

Jackson

et al. 2017

Inhalation Toxicology

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“…Interestingly, comparative studies between epithelial cell lines (BEAS-2B and A549) and such differentiated ALI cultures show that these primary cultures may be more resistant to the toxic effects than cell lines . In addition to various studies using investigator-established ALI airway epithelial cell cultures (Zarcone et al, 2016;Aug et al, 2015), also these commercial ALI systems have been applied in in vitro toxicology studies (Reus et al, 2014;Kuper et al, 2015;Neilson et al, 2015). As an alternative to ALI culture, rotating bioreactors have been developed in which epithelial monolayers are alternately submerged in culture media or exposed to air on the apical side (Raredon et al, 2015).…”

Section: Primary Lung Epithelial Cellsmentioning

confidence: 99%

Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

Hiemstra

Grootaers

Does

et al. 2018

Toxicology in Vitro

153

116

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A B S T R A C TThe epithelium that covers the conducting airways and alveoli is a primary target for inhaled toxic substances, and therefore a focus in inhalation toxicology. The increasing concern about the use of animal models has stimulated the development of in vitro cell culture models for analysis of the biological effects of inhaled toxicants. However, the validity of the current in vitro models and their acceptance by regulatory authorities as an alternative to animal models is a reason for concern, and requires a critical review. In this review, focused on human lung epithelial cell cultures as a model for inhalation toxicology, we discuss the choice of cells for these models, the cell culture system used, the method of exposure as well as the various read-outs to assess the cellular response. We argue that rapid developments in the 3D culture of primary epithelial cells, the use of induced pluripotent stem cells for generation of lung epithelial cells and the development of organ-on-a-chip technology are among the important developments that will allow significant advances in this field. Furthermore, we discuss the various routes of application of inhaled toxicants by air-liquid interface models as well as the vast array of read-outs that may provide essential information. We conclude that close collaboration between researchers from various disciplines is essential for development of valid methods that are suitable for replacement of animal studies for inhalation toxicology.

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“…For example, the Vitrocell V R 24/48 ALI exposure system has been extensively used to evaluate the toxicity of cigarette smoke (Iskandar et al, 2013;Mathis et al, 2013;Schlage et al, 2014) as well as electronic cigarette aerosols (Neilson et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract

Nordlund

Bělka

Kuczaj

et al. 2017

Inhalation Toxicology

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Inhalation of aerosols generated by electronic cigarettes leads to deposition of multiple chemical compounds in the human airways. In this work, an experimental method to determine regional deposition of multicomponent aerosols in an in vitro segmented, realistic human lung geometry was developed and applied to two aerosols, i.e. a monodisperse glycerol aerosol and a multicomponent aerosol. The method comprised the following steps: (1) lung cast model preparation, (2) aerosol generation and exposure, (3) extraction of deposited mass, (4) chemical quantification and (5) data processing. The method showed good agreement with literature data for the deposition efficiency when using a monodisperse glycerol aerosol, with a mass median aerodynamic diameter (MMAD) of 2.3 lm and a constant flow rate of 15 L/min. The highest deposition surface density rate was observed in the bifurcation segments, indicating inertial impaction deposition. The experimental method was also applied to the deposition of a nebulized multicomponent aerosol with a MMAD of 0.50 lm and a constant flow rate of 15 L/min. The deposited amounts of glycerol, propylene glycol and nicotine were quantified. The three analyzed compounds showed similar deposition patterns and fractions as for the monodisperse glycerol aerosol, indicating that the compounds most likely deposited as parts of the same droplets. The developed method can be used to determine regional deposition for multicomponent aerosols, provided that the compounds are of low volatility. The generated data can be used to validate aerosol deposition simulations and to gain insight in deposition of electronic cigarette aerosols in human airways. ARTICLE HISTORY

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Development of an in vitro cytotoxicity model for aerosol exposure using 3D reconstructed human airway tissue; application for assessment of e-cigarette aerosol

Cited by 124 publications

References 52 publications

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

A comparative study of electronic cigarette vapor extracts on airway-related cell lines in vitro

Human lung epithelial cell cultures for analysis of inhaled toxicants: Lessons learned and future directions

Multicomponent aerosol particle deposition in a realistic cast of the human upper respiratory tract

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