An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D differentiated co-culture model of human airways

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Currently there is a lack of consensus on the possible adverse health effects of E-cigarettes (ECs). Important factors including cell model employed and exposure method determine the physiological relevance of EC studies. The present study aimed to evaluate EC cytotoxicity using a physiologically relevant in-vitro multicellular model of human airways.
Human bronchial epithelial cells (CALU-3) and pulmonary fibroblasts (MRC-5) were co-cultured at air-liquid-interface for 11-14 days post which they were exposed to whole cigarette smoke (WCS) or EC vapour (ECV) at standard ISO-3308 regime for 7 m using a bespoke aerosol delivery system. ECV effects were further investigated at higher exposure times (1 h – 6 h).
Results showed that while WCS significantly reduced cell viability after 7 m, ECV decreased cell viability only at exposure times higher than 3 h. Furthermore, ECV caused elevated IL-6 and IL-8 production despite reduced cell viability. ECV exposure also produced a marked increase in oxidative stress. Finally, WCS but not ECV exposure induced caspase 3/7 activation, suggesting a caspase independent death of ECV exposed cells.
Overall, our results indicate that prolonged ECV exposure (≥ 3 h) has a significant impact on pro-inflammatory mediators’ production, oxidative stress and cell viability but not caspase 3/7 activity.



Original languageEnglish
Pages (from-to)255-264
JournalToxicology in Vitro
Early online date27 Jun 2018
Publication statusE-pub ahead of print - 27 Jun 2018

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© 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International


  • E-cigarette, Cytotoxicity, Co-culture model, Human airways, Multi-cellular, CALU 3, In-vitro

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