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

Vasanthi Bathri Narayanan, Pranav, Brown, James E, Marshall, Lindsay and Leslie, Laura J (2018). An investigation into E-cigarette cytotoxicity in-vitro using a novel 3D differentiated co-culture model of human airways. Toxicology in Vitro, 52 , pp. 255-264.


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.

Publication DOI:
Divisions: Engineering & Applied Sciences
Engineering & Applied Sciences > Mechanical Engineering & Design
Engineering & Applied Sciences > Aston Institute of Materials Research (AIMR)
Life & Health Sciences > Biosciences
Life & Health Sciences > Cell & Tissue Biomedical Research
Life & Health Sciences
Life & Health Sciences > Chronic and Communicable Conditions
Additional Information: © 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Uncontrolled Keywords: E-cigarette,Cytotoxicity,Co-culture model,Human airways,Multi-cellular,CALU 3,In-vitro
Full Text Link:
Related URLs: https://www.sci ... 887233318302960 (Publisher URL)
Accepted Date: 2018-06-21
Published Online Date: 2018-06-27
Authors: Vasanthi Bathri Narayanan, Pranav
Brown, James E ( 0000-0002-3504-7373)
Marshall, Lindsay
Leslie, Laura J ( 0000-0002-7925-9589)

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