bFGF reverses the immunosuppressive effect of mesenchymal stem cells licensed by inflammatory cytokines

Mesenchymal stem cells (MSCs) have been shown to possess a superb ability to suppress vigorous immune responses through a concerted action of chemokines and nitric oxide (NO) induced by proinflammatory cytokines. This immunoregulatory effect of MSCs is plastic and varies according to the status of the tissue microenvironments where they reside. We report herein that basic fibroblast growth factor (bFGF) is effective in reversing the powerful immunosuppressive effect of MSCs induced by IFNγ and TNFα. This ability of bFGF was found to be due to its inhibition on inducible NO synthase (iNOS) expression and subsequent NO production. Using a specific inhibitor PD173074 and targeting siRNA, we demonstrated that bFGF directly acts on MSCs by binding to FGFR1. We further found that the autocrine bFGF could reduce iNOS expression and NO production in IFNγ and TNFα treated MSCs. Thus, our study revealed a novel mechanisms through which bFGF dramatically affects the inflammatory status of the tissue microenvironment by reversing the immunosuppressive effect of MSCs. Targeting bFGF and its signalling pathway could be a novel strategy to enhance the efficiency of MSC-based treatment of inflammatory diseases.