Human primary mesenchymal stem cells fail to recover full osteogenic differentiation potential following washout of electronic cigarette aerosol extracts.

Abstract

Electronic cigarettes (e-cigarettes) are promoted as safer alternatives to combustible cigarettes. However, the health burden and effects of their long-term use remain unidentified. This study evaluates the extent and reversibility of cellular damage in human bone marrow-derived mesenchymal stem cells (MSCs), following in vitro exposure to cigarette and e-cigarette smoke aerosols. Human primary MSCs were seeded and exposed to combustible or e-cigarette smoke aerosol extracts for 2 or 3 weeks. MSCs were then assessed for survival and membrane protein expression and distribution. In addition, osteogenic differentiation potential was examined after addition of a differentiation cocktail made up of dexamethasone, ascorbic acid and β-glycerophosphate. MSC-mediated cellular repair, described in terms of MSC proliferation and osteogenic differentiation, was compromised by both cigarette and e-cigarette aerosol extracts. MSCs exhibited partial recovery of their proliferative ability after smoke washout. Their membrane proteins were downregulated and their distribution was altered on the plasma membrane. MSCs showed signs of early osteogenic differentiation following washout of e-cigarette, but matrix mineralization (indicative of terminal differentiation) was hampered, similarly to combustible cigarette aerosols. These results provide insights on the safety of e-cigarettes and the potential risks they pose to regenerative health, help explain impaired tissue repair mechanisms in chronic smokers, and can serve to inform future public policies on tobacco control.