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首页> 外文期刊>The journal of gene medicine >Transplantation of CTLA_4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis
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Transplantation of CTLA_4Ig gene-transduced adipose tissue-derived mesenchymal stem cells reduces inflammatory immune response and improves Th1/Th2 balance in experimental autoimmune thyroiditis

机译：CTLA_4Ig基因转导的脂肪组织间充质干细胞的移植减少炎性免疫反应并改善实验性自身免疫性甲状腺炎的Th1 / Th2平衡

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Background Autoimmune thyroiditis is one of common organ-specific autoimmune disease. The aim of this study was to observe the effect of adipose tissue derived mesenchymal stem cells (ATMSC) and CTLA4Ig genetransduced ATMSC on autoimmune thyroiditis. Methods Experimental autoimmune thyroiditis was induced by immunization with thyroglobulin. Animals were divided into three groups: (i) a half million of human ATMSC, (ii) a half million of murine CLTA4Ig gene-transduced human ATMSC (CTLA4Ig-MSC), or (iii) normal saline (as control), which were administered intravenously four times within a 3-week period. Blood and tissue samples were collected 1 week after the last cell transplantation. Results The absorbance of serum thyroglobulin autoantibody (TgAA) in the CTLA4Ig-MSC group was considerably lower than those in other groups. In culture supernatant of LPS-stimulated spleen cells, both of the MSC-treated groups showed significantly lower absorbances of TgAA than the control. Flow cytometric analysis of spleen cells revealed a significant decrease in the proportion of CD3+ and CD11b in the CTLA4Ig-MSC group compared to the other groups. Lymphocyte infiltration in the thyroid glands was also dramatically decreased in both of MSC-treated groups. Cytokine analysis showed that ATMSC decreased the production of proinflammatory cytokines and improved the Th1/Th2 balance by down-regulating Th1 cytokines. Conclusion Although CTLA4Ig-MSC transplantation had better result in reduction of serum TgAA, both of ATMSC and CTLA4Ig-MSC transplantations are promising treatments for autoimmune thyroiditis judging from the results of histopathology and cytokine analysis. They may be attractive candidates for treating organ-specific autoimmune disease.
机译：背景自身免疫性甲状腺炎是常见的器官特异性自身免疫性疾病之一。这项研究的目的是观察脂肪组织来源的间充质干细胞（ATMSC）和CTLA4Ig基因转导的ATMSC对自身免疫性甲状腺炎的作用。方法用甲状腺球蛋白免疫诱导实验性自身免疫性甲状腺炎。将动物分为三组：（i）50万人类ATMSC，（ii）50万鼠类CLTA4Ig基因转导的人类ATMSC（CTLA4Ig-MSC），或（iii）生理盐水（作为对照），分别为在3周内静脉内给药4次。最后一次细胞移植后1周收集血液和组织样品。结果CTLA4Ig-MSC组血清甲状腺球蛋白自身抗体（TgAA）的吸收率明显低于其他组。在LPS刺激的脾细胞的培养上清液中，两个MSC处理组的TgAA吸光度均显着低于对照组。脾细胞的流式细胞术分析显示，与其他组相比，CTLA4Ig-MSC组中CD3 +和CD11b的比例显着降低。在两个MSC治疗组中，甲状腺中的淋巴细胞浸润也显着减少。细胞因子分析表明，ATMSC通过下调Th1细胞因子来减少促炎细胞因子的产生并改善Th1 / Th2平衡。结论尽管CTLA4Ig-MSC移植降低血清TgAA效果更好，但从组织病理学和细胞因子分析的结果来看，ATMSC和CTLA4Ig-MSC移植均是治疗自身免疫性甲状腺炎的有希望的方法。它们可能是用于治疗器官特异性自身免疫疾病的有吸引力的候选人。

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