OBJECTIVES: The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies. METHODS: CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring. The frequencies of lymphocytes in spleen were analysed, and serum concentrations of cytokines and autoantibody to CII were also measured. 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, which was comparable to biologic treatments. All the treatments down-regulated Th1 subset. Except anti-CD20 all the treatments decreased Th17 subset. MSC treatment enhanced the proportion of regulatory T (Treg) cells and inhibited the generation of T follicular helper (Tfh) cells. The decrease in autoantibody level was detectable in all the treated groups. In vitro MSC induced Foxp3+ T cells, and down-regulated IL-17+, IFNγ+ T cells and pathogenic IL-17+IFNγ+ or IL-17+Foxp3+ T cells. MSC also reduced the secretion of IL-1β, IL-6, IL-17 and TNF-α among collagen-specific T cells. CONCLUSIONS: MSC show comparable effects to the known biologic treatments and correct immune imbalance in CIA. MSC might provide a promising approach for the treatment of rheumatoid arthritis.
OBJECTIVES: The effects of mesenchymal stem cell (MSC) transplantation on established collagen-induced arthritis (CIA) were evaluated and compared to biologic therapies. METHODS: CIA was induced with the immunisation of type II collagen (CII) in DBA/1 mice. Human umbilical cord MSC, anti-TNF antibody, rhTNFR:Fc fusion protein and anti-CD20 antibody were respectively injected intraperitoneally into CIA mice. Arthritis severity was assessed by clinical and histological scoring. The frequencies of lymphocytes in spleen were analysed, and serum concentrations of cytokines and autoantibody to CII were also measured. 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, which was comparable to biologic treatments. All the treatments down-regulated Th1 subset. Except anti-CD20 all the treatments decreased Th17 subset. MSC treatment enhanced the proportion of regulatory T (Treg) cells and inhibited the generation of T follicular helper (Tfh) cells. The decrease in autoantibody level was detectable in all the treated groups. In vitro MSC induced Foxp3+ T cells, and down-regulated IL-17+, IFNγ+ T cells and pathogenic IL-17+IFNγ+ or IL-17+Foxp3+ T cells. MSC also reduced the secretion of IL-1β, IL-6, IL-17 and TNF-α among collagen-specific T cells. CONCLUSIONS: MSC show comparable effects to the known biologic treatments and correct immune imbalance in CIA. MSC might provide a promising approach for the treatment of rheumatoid arthritis.
Authors: Rui-Juan Cheng; An-Ji Xiong; Yan-Hong Li; Shu-Yue Pan; Qiu-Ping Zhang; Yi Zhao; Yi Liu; Tony N Marion Journal: Front Cell Dev Biol Date: 2019-11-15