Immunosuppressive effects of mesenchymal stem cells in collagen-induced mouse arthritis.

Objective The objective of this study was to investigate the efficacy of mesenchymal stem cell (MSC) in the treatment of arthritis. Methods Mesenchymal stem cells were injected intravenously into mice with collagen-induced arthritis (CIA). Arthritic indexes were evaluated, and the levels of the proand anti-inflammatory cytokines interleukin-10 (IL-10), gamma interferon (IFN-γ)-inducible protein 10 (IP-10), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-17A (IL-17A), and tumor necrosis factor α (TNF-α) in serum or splenic cells were determined using real-time RT-PCR, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The proliferation of dendritic cell line D2SC cells was determined using ³H-TdR incorporation assay. Results Upon injection of MSCs, overall arthritis symptoms were significantly improved in the CIA mouse models as indicated by the paw edema. Consistent with this observation, serum levels of pro-inflammatory cytokine TNF-α and inflammatory cell infiltration decreased significantly 12 days after MSC injection, while the expression of anti-inflammatory cytokines IL-10, IP-10, and CXCR3 was increased in splenocytes. In addition, we provided evidence that MSCs may directly promote the proliferation of D2SC cells and the expression of IP-10 in D2SC cells in vitro. Conclusion Mesenchymal stem cells significantly enhance the efficacy of collagen-induced arthritis treatment, likely through the modulation of the expression of various cytokines. [ABSTRACT FROM AUTHOR]