[Acetylsalicylic acid treatment enhanced immunomodulatory function of mesenchymal stem cells derived from gingiva]

Abstract

Objective: To analyze the role of acetylsalicylic acid (ASA) in immunomodulation of mesenchymal stem cells derived from gingiva (GMSCs), and to explore the role of ASA in enhancing the immumomodulation of GMSCs and the capacity of GMSCs to treat immune disorders and the underlying mechanism.

Methods: Flow cytometry analysis were used to analyze the role of ASA in the expression of stem cells surface markers CD146, CD105, CD90, CD34 and CD45 in GMSCs,and the GMSCs proliferation was analyzed by 5-bromo-2-deoxyuridine (BrdU) staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The GMSCs and T cells co-culture system was established to analyze the role of ASA in immunomodulation of GMSCs by measuring T cell apoptosis using flow cytometry analysis and inflammatory cytokines using enzyme linked immunosorbent assay (ELISA). Further more, the dextran sulfate sodium (DSS) induced colitis mouse model was established and the mouse body weight, disease activity score, histological index and pathological change of colons were analyzed after GMSC infusion.

Results: The proliferation of GMSCs and the expressions of CD105, CD146 in GMSCs were increased after ASA treatment. In the GMSCs and T cells co-culture system, GMSCs induced T cells apoptosis and inhibited interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) secretion by T cells, which were enhanced by ASA treatment. In vivo, GMSCs infusion could ameliorate DSS-induced colitis, including inhibited DSS-induced mouse body weight loss, decreased disease activity score and histological index, and decreased inflammation cells infiltration in colons, as shown by hematoxylin-eosin (HE) staining. Moreover, the therapeutic effects of GMSC infusion on DSS-induced colitis could be enhanced by ASA treatment. Mechanically, ASA treatment increased FasL expression of Fas/FasL death pathway in GMSCs to induce T cells apoptosis.

Conclusion: ASA enhanced immunomodulation of GMSCs and increased the capacity of GMSCs to ameliorate DSS-induced colitis in mice.