Background/Purpose Tremendous progress has been made in the development of non-conventional therapies for rheumatoid arthritis (RA). In this study, the effects of mesenchymal stem cells (MSCs) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared with two kinds of biologic agents, anti-tumor necrosis factor (TNF) and anti-CD20 antibody.

Methods CIA was induced with the immunization of type II collagen (CII) and CFA in DBA/1J mice. Human umbilical cord derived MSCs (5×10⁶), anti-TNF antibody (100ug) and anti-CD20 antibody (200ug) were intraperitoneally injected into 3 groups of mice on day 28 after the immunization. The control group was treated with human fibroblasts (5×10⁶). All mice were sacrificed 3 weeks later and arthritis severity was assessed by clinical and histology scoring. The frequency of CD4+ T cell subsets, B cells and plasma cells in spleen was analyzed by flow cytometry. Serum levels of autoantibody to mouse CII were determined by ELISA. The ability of MSCs to modulate Treg/Th17 cell percentages in CD3/CD28 stimulated DBA/1J T cells was assessed in vitro.

Results MSCs treatment significantly decreased the severity of arthritis and pathology scores, which was comparable to anti-TNF or anti-CD20 treatment. Anti-CD20 treatment depleted nearly half of B220+ cells, and markedly reduced the frequency of plasma cells and serum levels of autoantibody compared to the control group (738±187 vs. 1817±447 U/ml, p<0.001). The decrease of autoantibody level was also detectable in those with anti-TNF treatment (663±336 U/ml) and MSCs treatment (1057±362 U/ml), but neither of these two treatments had an impact on the percentage of B cells or plasma cells. All of the three treatments resulted in a decrease in Th1 subset, but none of them altered the percentage of Th2 subset. Except anti-CD20 treatment, both MSCs and anti-TNF treatment significantly decreased the percentages of Th17 cells. Notably, only MSCs treatment increased the percentages of regulatory T cells (11.39±0.85 % vs 7.37±1.82 % in the control group, p<0.01). In vitro study confirmed that MSCs could induce the generation of Foxp3+ T cells but reduce the percentages of pathogenic IL-17+Foxp3+ T cells.

Conclusion MSCs exerted comparable therapeutic effects as biological agents on CIA through different mechanisms. MSCs may provide a promising approach for the treatment of RA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/therapeutic-effects-of-mesenchymal-stem-cells-anti-tumor-necrosis-factor-and-anti-cd20-treatment-on-collagen-induced-arthritis/