| Summary: | Introduction
Mesenchymal stromal cells (MSCs) play a crucial role in promoting
tissue regeneration and healing, particularly in bone tissue. Both smoking and
nicotine use are known to delay and inhibit the healing process in patients. This
study aims at delineating these cellular effects by comparing the impact of nicotine
alone to cigarette smoke with equivalent nicotine content, and shedding light on
potential differences in the healing process.
Methods
We examined how cigarette smoke and nicotine affect the migration,
proliferation, and osteogenic differentiation of human patient-derived MSCs in
vitro , as well as the secretion of cytokines IL-6 and IL-8. We measured nicotine
concentration of the cigarette smoke extract (CSE) to clarify the role of the
nicotine in the effect of the cigarette smoke.
Results
MSCs exposed to nicotine-concentration-standardized CSE exhibited
impaired wound healing capability, and at high concentrations, increased cell
death. At lower concentrations, CSE dose-dependently impaired migration,
proliferation, and osteogenic differentiation, and increased IL-8 secretion. Nicotine
impaired proliferation and decreased PINP secretion. While there was a trend for
elevated IL-6 levels by nicotine in undifferentiated MSCs, these changes were not
statistically significant. Exposure of MSCs to equivalent concentrations of nicotine
consistently elicited stronger responses by CSE and had a more pronounced effect
on all studied parameters. Our results suggest that the direct effect of cigarette
smoke on MSCs contributes to impaired MSC function, that adds to the nicotine
effects.
Conclusions
Cigarette smoke extract reduced the migration, proliferation, and
osteogenic differentiation in MSCs in vitro , while nicotine alone reduced
proliferation. Cigarette smoke impairs the osteogenic and regenerative ability
of MSCs in a direct cytotoxic manner. Cytotoxic effect of nicotine alone impairs
regenerative ability of MSCs, but it only partly explains cytotoxic effects of
cigarette smoke. Direct effect of cigarette smoke, and partly nicotine, on MSCs
could contribute to the smoking-related negative impact on long-term bone
health, especially in bone healing.
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