Background: Gingiva-derived mesenchymal stem cells (GMSCs) suppress immune and inflammatory responses in experimental arthritis models. Here, we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs). Methods: Surface markers of GMSCs were analyzed by flow cytometry. mRNA expression of matrix metalloproteinases and pro-inflammatory cytokine in RA FLSs was measured by quantitative polymerase chain reaction (PCR). RA FLS proliferation was analyzed by a 5-ethynyl-2′-deoxyuridine assay. To explore the molecular mechanisms, we assessed the effect of GMSCs on RA FLS proliferation by adding indoleamine-2,3-dioxygenase (IDO), CD39, or CD73 inhibitors. The invasion was analyzed by a transwell assay. The anti-inflammatory effects of GMSCs were assessed in a type II collagen-induced arthritis (CIA) mouse model. Results: Compared with human dermal fibroblast, GMSCs displayed a higher expression of CD39. Interleukin (IL)-8, IL-6, MMP-1, MMP-3, MMP-13, and monocyte chemoattractant protein-1 mRNA were all decreased in RA FLSs after incubation with GMSCs. GMSCs significantly reduced RA FLS proliferation in a dose-dependent manner in vitro, which was partly dependent on CD39/CD73 signaling. GMSCs significantly impeded the invasive capacity of RA FLSs in a dose-dependent manner in vitro. GMSCs infusion delayed arthritis onset and reduced arthritis scores in the CIA model. Conclusion: GMSCs are effective to inhibit the aggressive behavior of RA FLSs and treat experimental arthritis, implying their therapeutic potential in RA patients.
K E Y W O R D SGingiva-derived mesenchymal stem cells, rheumatoid arthritis, type II collagen-induced arthritis
Key points• Gingiva-derived mesenchymal stem cells (GMSCs) suppress the proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs) from RA patients. • GMSCs are effective in treating experimental arthritis.