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

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Abstract

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-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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (no. 30840053, 30471938), Jiangsu Province’s Outstanding Medical Academic Leader Program (no. LJ200614), the Natural Science Foundation of the Jiangsu Province (no. BK2007705, BK2007092, and BK2008232), the Social Development Foundation of Zhenjiang (no. SH2008070), Sci-tech Innovation Team and Talents of Jiangsu University (no. 2008-018-02), and Jiangsu Public Technology Service Platform of Stem Cells and Biotherapy (no. BM2008146).

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Correspondence to Wen-Rong Xu.

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Responsible Editor: J. Di Battista.

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Mao, F., Xu, WR., Qian, H. et al. Immunosuppressive effects of mesenchymal stem cells in collagen-induced mouse arthritis. Inflamm. Res. 59, 219–225 (2010). https://doi.org/10.1007/s00011-009-0090-y

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  • DOI: https://doi.org/10.1007/s00011-009-0090-y

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