THU0037 Comparable Therapeutic Potential of Umbilical Cord Mesenchymal Stem Cells in Collagen Induced Arthritis with Anti-Tumor Necrosis Factor or Anti-CD20
Authors: Y. Sun, W. Kong, W. Chen, G. Yao, X. Feng, L. Sun
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Tremendous progress has been made in the development of non-conventional therapies for rheumatoid arthritis (RA). Mesenchymal stem cells (MSC) present multiple immunosuppressive capacities and may have the potential to exert therapeutic effect in RA. <h3>Objectives</h3> In this study, the effects of MSC 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. <h3>Methods</h3> CIA was induced with the immunization of type II collagen (CII) in DBA/1 mice. Human umbilical cord derived MSC (5×10<sup>6</sup>), anti-TNF antibody (100μg) and anti-CD20 antibody (200μg) were injected i.p. into mice on day 28 after the immunization, respectively. The control group was treated with PBS or human fibroblasts (5×10<sup>6</sup>). All mice were sacrificed 3 weeks later and arthritis severity was assessed by clinical and histology scoring. The frequency of CD4<sup>+</sup> T cell subsets, B cells and plasma cells in spleen was analyzed by flow cytometry. Serum levels of autoantibody to mouse CII were also determined. The ability of MSC to regulate the balance of T helper cell subsets in CII stimulated CIA CD4<sup>+</sup> T cells was assessed <i>in vitro</i>. <h3>Results</h3> MSC treatment significantly decreased the severity of arthritis and pathology scores, which was comparable to anti-TNF or anti-CD20 treatment. 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 MSC and anti-TNF treatment significantly decreased Th17 subset. Anti-CD20 treatment depleted nearly half of B220<sup>+</sup> cells, and markedly reduced the frequency of plasma cells and serum levels of autoantibody compared to the control group [(738±187) U/ml vs (1817±447) U/ml, <i>P</i>&lt;0.001]. The decrease of autoantibody level was also detectable in the group of anti-TNF treatment (663±336 U/ml) or MSC treatment (1057±362 U/ml), but neither of these two treatments showed significant effect on the percentage of B cells or plasma cells. MSC inhibited the generation of T follicular helper (Tfh) cells which play a key role for supporting B cells and antoantibody production. MSC treatment also enhanced the proportion of regulatory T (Treg) cells compared to the control group. <i>In vitro</i> MSC inhibited the generation of IL17<sup>+</sup> or IFNγ<sup>+</sup> T cells, induced Foxp3<sup>+</sup> T cells, and also reduced pathogenic IL17<sup>+</sup>IFNγ<sup>+</sup> or IL-17<sup>+</sup>Foxp3<sup>+</sup> T cells. <h3>Conclusions</h3> These results indicated that MSC may have a role in preventing the pathogenic plasticity of CD4<sup>+</sup> T cell subsets in arthritic milieu. Umbilical cord (UC)-MSC could exert comparable effects to biologic agents and effectively correct the immune imbalance in CIA. UC-MSC may provide a promising approach for the treatment of RA. <h3>Disclosure of Interest</h3> None declared