The Therapeutic Effect Of Xenogenic MSCs Derived From Bone Marrow On Experimental Autoimmune Thyroiditis By Influening Th1/Th2Cells Balance

Objective:To study the effect of bone marrow mesenchymal stem cells(MSCs) on experimental autoimmune thyroiditis(EAT) and discuss the immuno-regulatory mechanism of Thl/Th2cytokine imbalance by detecting concentration of interleukine-10(IL-10) and interferon-γ (IFN-γ) in the serum of all the models.Methods:Bone marrow mesenchymal stem cells (BMSCs) were obtained from wistar rats thighbone under aseptic condition, then cultured and pured by the whole marrow-cultured method.Immunohistochemistry was applied to detect cell-surface marker expressions:CD29, CD44, CD34and CD45, which help to identify BMSCs.36female C57BL/6mice were randomly divided into three groups:normal control (A), EAT model (B), MSCs intervention treatment(C), n=12. The groups of B, C immunized with thyroglobulin (Tg) at day0,14to establish the model of EAT; Group A was injected with the same dose of saline at the same time. Group C was injected by caudal vein with xenogenic MSCs3×105/150ul at day0,7,14,21; Group A, B was injected with the same dose of saline at the same time.All mice were killed at the28th day after primary immunity. The level of TgAb, TPOAb, TmAb, TT3, TT4, IFN-γ,IL-10was detected and pathological changes in thyroid tissue were observed.Results:1. Group A showed that thyroid follicular was mature and no infiltration of inflammatory cells were showed under pathological examination; The thyroid in Group B and C showed inflammatory response and inflammatory cells infiltration, but the response in group C was weaker than group B.2. The level of TgAb, TPOAb, TmAb in Group B compared with Group A was increased, after treatment with BMSCs,Group C was lower, the difference was significant(P<0.01);but Group C compared with Group A was significant too. 3. The level of TT4in Group B compared with Group A was lower, after treatment with BMSCs, Group C was increased,the difference was significant(P<0.05); the difference of TT3was not significant between Group A, Group B and Group C.4. The level of IFN-γ was increased, and the level of IL-10was lower,the ratio of IFN-γ/IL-10was increased in Group B compared with Group A, but after treatment with BMSCs, the level of IFN-γ was lower, and the level of IL-10was increased, the ratio of IFN-γ/IL-10was lower in Group C, the difference was significant (P<0.05);Conclusion:1. The model of EAT to establish with PTg and freund adjuvant is successful. The thyroid in Group B showed inflammatory response and inflammatory cells infiltration, and the level of TgAb, TPOAb, TmAb was increased compared with Group A.2. MSCs are easy to grow and be cultured in vitro, have a low immunogenicity, and there are no untoward effect after infusion with xenogenic MSCs.3. The response of inflammatory cells infiltration in group C was weaker than group B, and the level of TgAb, TPOAb, TmAb in Group C compared with Group B was lower,indicating that MSCs can inhibit the production of inflammation, lymphocyte infiltration, autoantibody in thyroid and has a positive treatment effect to Hashimoto thyroiditis (HT).4. The level of IFN-γ was increased, the level of IL-10was lower,the ratio of IFN-γ/IL-10was increased in Group B compared with Group A; after treatment with BMSCs, the level of IFN-γ was lower, the level of IL-10was increased, the ratio of IFN-γ/IL-10was lower in Group C compared with Group B. Thus indicates the protective function of MSCs may be related to down regulation of Thl cytokine and up regulation of Th2cytokine, and may reduce the incidence of autoimmune polyglandular syn-drome.