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Abstract Number: 2343

Therapeutic Effects of Mesenchymal Stem Cells, Anti-Tumor Necrosis Factor and Anti-CD20 Treatment on Collagen Induced Arthritis

Yue Sun1, Xuebing Feng2 and Lingyun Sun2, 1The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China, 2Department of Rheumatology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: anti-TNF therapy, mesenchymal stem cells and rheumatoid arthritis (RA)

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Session Information

Session Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

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.


Disclosure:

Y. Sun,
None;

X. Feng,
None;

L. Sun,
None.

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