Electronic cigarettes (e-cigarettes) were originally designed as an alternative to conventional smoking to aid smokers in quitting and to reduce the negative impacts on their health. However, in recent years, the use of e-cigarettes (vaping) has become increasingly popular with non-smokers, with an estimated 41 million e-cigarette users in 2018. Although vaping is considered to be relatively healthier than smoking, increasing incidence of vaping-associated lung injuries has highlighted the requirement for research investigating the impact of vaping on the airways.

To address this, Thibeault and colleagues previously developed a human induced pluripotent stem cell (hiPSC)-derived three-dimensional (3D) model of vocal fold (VF) mucosae. This in vitro model recapitulates the human VF mucosal epithelium and its remodelling response to damage. In this study, the authors utilised this model to assess the impact of exposure to e-cigarette vapour extract (ECVE) on epithelial health and regeneration. They found that exposure of VF mucosae to 0.5% or 5% ECVE for 1 week disrupted epithelial homeostasis, including altered expression of mucosal and innate immune response proteins. VF luminal cells were also damaged and intracellular lipid aggregates accumulated in these cells, evidencing inefficient clearance of lipids and solvents, which consequently perturbed lipid metabolism and plasma membrane properties.

The authors then assessed VF epithelial responses after 1, 3 and 7 days of regeneration following the week of ECVE exposure. Significant epithelial remodelling was observed, including the expansion of basal cells and increased deposition of proteins that can lead to basal cell hyperplasia, hyperkeratinisation and basement membrane thickening. These reactive epithelial changes were accompanied by increased expression of genes of the Wnt/β-catenin signalling pathway, suggesting that this pathway might be involved in the regenerative response.

As vaping continues to increase in popularity, it is becoming more important to understand the impacts of vaping on our health. Here, Thibeault and colleagues have revealed the mechanisms of damage caused by vaping in mucosal cells and subsequent epithelial remodelling. This study highlights the hiPSC-derived VF model as a useful tool for future studies, which will be required to fully assess the safety concerns of vaping to ultimately inform health policy decision making.

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