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 pro- and anti-inflammatory cytokines interleukin-10 (IL-10), gamma interferon (IFN-gamma)-inducible protein 10 (IP-10), chemokine (C-X-C motif) receptor 3 (CXCR3), interleukin-17A (IL-17A), and tumor necrosis factor alpha (TNF-alpha) 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 (3)H-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-alpha 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.