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Electronic Cigarette Smoke Impairs Normal Mesenchymal Stem Cell Differentiation.

ABSTRACT: Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigarettes. However, the effects of chronic inhalation of potential toxicants emitted by ecigarettes remain largely unexamined. It is conceivable that smoking-induced chronic diseases result in cellular injury, in the absence of effective repair by stem cells. This study evaluates the effect of cigarette and e-cigarette aerosol extracts on the survival and differentiation of bone marrow-derived mesenchymal stem cells (MSCs). MSC growth and osteogenic differentiation were examined after exposure to smoke extracts. Data revealed detrimental effects of both cigarette and e-cigarette extracts on MSC morphology and growth. Levels and activity of alkaline phosphatase, an osteogenic marker, decreased and induction of osteoblastic differentiation was impaired. Both smoke extracts prevented osteogenic differentiation from progressing, evident by decreased expression of terminal osteogenic markers and mineralization. Elevated levels of reactive oxygen species (ROS) were detected in cells exposed to smoke extracts. Moreover, decreased differentiation potential was concomitant with severe down-regulation of Connexin 43 expression, leading to the loss of gap junction-mediated communication, which together with elevated ROS levels, could explain decreased proliferation and loss of differentiation potential. Hence, e-cigarettes present similar risk as combustible cigarettes with respect to tissue repair impairment.

SUBMITTER: Shaito A

PROVIDER: S-EPMC5660168 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Electronic Cigarette Smoke Impairs Normal Mesenchymal Stem Cell Differentiation.

Shaito A A Saliba J J Husari A A El-Harakeh M M Chhouri H H Hashem Y Y Shihadeh A A El-Sabban M M

Scientific reports 20171027 1

Electronic cigarettes (e-cigarettes) are promoted as low-risk alternatives to combustible cigarettes. However, the effects of chronic inhalation of potential toxicants emitted by ecigarettes remain largely unexamined. It is conceivable that smoking-induced chronic diseases result in cellular injury, in the absence of effective repair by stem cells. This study evaluates the effect of cigarette and e-cigarette aerosol extracts on the survival and differentiation of bone marrow-derived mesenchymal ...[more]

PMID: 29079789

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Project description:IntroductionMesenchymal 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.MethodsWe 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.ResultsMSCs 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.ConclusionsCigarette 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.

Project description:IntroductionCigarette smoking is the main risk factor for lung cancer. MSCs in the TME promoting tumor angiogenesis, growth, and metastasis. SIBLING proteins enable cancer cells to extend, invade and metastasize.ObjectivesCigarette smoke promotes the progression and metastasis of lung cancer, although how this occurs is poorly understood. We evaluated the impact of whether cigarette smoking motivates SIBLING protein expression and is involved in MSC-mediated lung tumor metastasis.MethodsWe investigated the expression of OPN in the Gene Expression Omnibus (GEO) databases and confirmed the results by immunohistochemistry (IHC), qPCR and Western blotting (WB) of lung cancer cells and tissues. The effect of OPN on the recruitment and adhesion of mesenchymal stem cells (MSCs) to lung cancer cells and lung cancers metastasis was investigated by Transwell, adhesion assays. A series of in vitro and in vivo experiments were conducted to demonstrate the mechanisms by which OPN modulates recruitment and adhesion of MSCs to lung cancer cells and lung cancer metastasis.ResultsCigarette smoke extract (CSE) and benzo[α]pyrene (B[α]P) increased levels of OPN expression and facilitated the recruitment and adhesion of MSCs to lung cancer cells via JAK2/STAT3 signaling. We also observed that OPN promotes tumor-associated MSC (TA-MSC) formation through the OPN receptor (integrins αvβ1, αvβ3, αvβ5 or CD44), inducing lung cancer cell migration and invasion. In an orthotopic mouse model of lung cancer, increases in OPN expression promoted by cigarette smoke upregulated MSC recruitment and facilitated lung cancer metastasis. Knockdown of OPN expression inhibited cigarette smoke-induced lung cancer metastasis in vivo.ConclusionCigarette smoke increases OPN expression through the JAK2/STAT3 signaling pathway to attract MSC cell recruitment and promote lung cancer metastasis. Our findings offer important insights into how lung cancer metastasis develops in smokers.

Project description:The strong relationship between cigarette smoking and cardiovascular disease (CVD) has been well-documented, but the mechanisms by which smoking increases CVD risk appear to be multifactorial and incompletely understood. Mesenchymal stem cells (MSCs) are regarded as an important candidate for cell-based therapy in CVD. We hypothesized that MSCs derived from induced pluripotent stem cell (iPSC-MSCs) or bone marrow (BM-MSCs) might alleviate cigarette smoke (CS)-induced cardiac injury. This study aimed to investigate the effects of BM-MSCs or iPSC-MSCs on CS-induced changes in serum and cardiac lipid profiles, oxidative stress and inflammation as well as cardiac function in a rat model of passive smoking. Male Sprague-Dawley rats were randomly selected for exposure to either sham air (SA) as control or 4% CS for 1 h per day for 56 days. On day 29 and 43, human adult BM-MSCs, iPSC-MSCs or PBS were administered intravenously to CS-exposed rats. Results from echocardiography, serum and cardiac lipid profiles, cardiac antioxidant capacity, cardiac pro- and anti-inflammatory cytokines and cardiac morphological changes were evaluated at the end of treatment. iPSC-MSC-treated group showed a greater effect in the improvement of CS-induced cardiac dysfunction over BM-MSCs-treated group as shown by increased percentage left ventricular ejection fraction and percentage fractional shortening, in line with the greater reversal of cardiac lipid abnormality. In addition, iPSC-MSCs administration attenuated CS-induced elevation of cardiac pro-inflammatory cytokines as well as restoration of anti-inflammatory cytokines and anti-oxidative markers, leading to ameliorate cardiac morphological abnormalities. These data suggest that iPSC-MSCs on one hand may restore CS-induced cardiac lipid abnormality and on the other hand may attenuate cardiac oxidative stress and inflammation via inhibition of CS-induced NF-?B activation, leading to improvement of cardiac remodeling and dysfunction. Thus, iPSC-MSCs may be a promising candidate in cell-based therapy to prevent cardiac complications in smokers.

Project description:BackgroundCigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation.MethodsWe developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated.ResultsSmoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression.ConclusionsOur findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a "smoke sensor" for bone remodeling.

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Electronic Cigarette Smoke Impairs Normal Mesenchymal Stem Cell Differentiation.

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Electronic Cigarette Smoke Impairs Normal Mesenchymal Stem Cell Differentiation.

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