Background 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.
Objectives 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.
Methods CIA was induced with the immunization of type II collagen (CII) in DBA/1 mice. Human umbilical cord derived MSC (5×106), 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 (5×106). 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 also determined. The ability of MSC to regulate the balance of T helper cell subsets in CII stimulated CIA CD4+ T cells was assessed in vitro.
Results 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+ 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, P<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. In vitro MSC inhibited the generation of IL17+ or IFNγ+ T cells, induced Foxp3+ T cells, and also reduced pathogenic IL17+IFNγ+ or IL-17+Foxp3+ T cells.
Conclusions These results indicated that MSC may have a role in preventing the pathogenic plasticity of CD4+ 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.
Disclosure of Interest None declared