Impact of Smoking On Immunomodulation Of Dental Pulp Stem Cells

Abstract

COVID‐19 has caused a global pandemic since 2019. After infecting the host cells, SARS‐CoV‐2 shows ability to hijack the host immune system and launch a cytokines‐storm. Smoking is reported to predispose patients to the respiratory system damage and lead to increased vulnerability to SARS‐CoV‐2 and more severe outcomes. Stem cells (SCs) are proposed as an alternative therapy of COVID‐19, especially the severe cases.Objectiveto investigate the impact of smoking and vaping on the inflammatory response of dental pulp stem cells (DPSCs).Hypothesiscigarette smoking and vaping inhibit the immunomodulatory, antimicrobial, and regenerative properties of the DPSCs and will reduce the success of stem cell therapy of COVID‐19.MethodsDPSCs were treated with various doses of cigarette smoke condensate (CSC) or nicotine for 24‐96 hours. Cell lysate and concentrated cell culture medium were collected at the end of the treatment. Expression of inflammatory cytokines were determined using human cytokine array, ELISA and quantitative PCR.Resultsthe level of TGF‐b2□ TGF‐b3, pulmonary and activation‐regulated chemokine (PARC or CCL‐18), tissue inhibitor of metalloproteinases (TIMP)‐1 and LIGHT (TNF superfamily member 14) significantly decreased after 48 hours exposed to 100mg/ml CSC. Interestingly, nicotine induced a different pattern of change of cytokine release. ELISA and quantitative PCR also showed that CSC treatment led to elevation of pro‐inflammatory cytokine IL‐6 level and reduction of anti‐inflammatory cytokine TGF‐b1 level in DPSC.Conclusionour current results indicated that smoking changes the cytokine expression profile in DPSCS, which has been used in clinical trials in treating COVID‐19. In addition to sharing many similarities with bone marrow mesenchymal SCs, DPSCs are also easy to access and show low immunogenicity reaction, making them valuable source to battle COVID‐19. We will further investigate the mechanism of how the SCs attenuate the cytokine storm induced by COVID‐19.