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Owing to their immunosuppressive properties mesenchymal stem cells (MSCs) are widely applicable in the treatment of autoimmune disease. The aim of this study was to investigate whether the indoleamine 2,3-dioxygenase-1 (IDO-1) and cyclooxygenase-2 (COX-2) genes enhanced the immunosuppressive functional ability of MSCs following stable transfection. To strengthen the immunomodulatory ability of MSCs, IDO-1 and COX-2 were overexpressed in umbilical cord progenitor cell-derived MSCs using recombinant plasmids and electroporation. RT-qPCR analysis and western blotting confirmed the expression of IDO-1 and COX-2 in transfected MSCs. Further functional assays in co-culture experiments, including lymphocyte proliferation and cyto-toxicity assays showed that COX-2-transfected MSCs possessed more potent immunomodulatory cells than the untreated MSCs, or MSCs transfected with IDO-1. Additionally, synthesis of interferon-γ and tumor necrosis factor-α (TNF-α) was significantly inhibited in lymphocytes co-cultured with COX-2-transfected MSCs, which was consistent with changes in immune-related genes in MSCs. An enhanced expression of IDO-1, COX-2, heme-oxygenase-1, inducible nitric-oxide synthase, TNF-α-stimulated gene/protein-6, transforming growth factor-β (TGF-β), human leukocyte antigen molecule 5 (HLA-G5) and interleukin-10 (IL-10) was identified following COX-2 transfection. We showed that the overexpression of COX-2 enhanced the immunosuppressive function of MSCs. COX-2-modified MSCs more potently inhibited the activation and proliferation of peripheral blood mononuclear cells.

international journal of molecular medicine

Overexpression of COX-2 but not indoleamine 2,3-dioxygenase-1 enhances the immunosuppressive ability of human umbilical cord-derived mesenchymal stem cells