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人羊膜间充质细胞移植可减轻胶原诱导性关节炎大鼠的疾病发展。

Transplantation of human amnion mesenchymal cells attenuates the disease development in rats with collagen-induced arthritis.

作者信息

Shu Jun, Pan Lin, Huang Xiaojie, Wang Ping, Li Hong, He Xiaojuan, Cai Zhe

机构信息

Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Clin Exp Rheumatol. 2015 Jul-Aug;33(4):484-90. Epub 2015 May 11.

Abstract

OBJECTIVES

Human amnion mesenchymal cells (hAMCs), isolated from the amniotic membrane of human placenta, are a unique population of mesenchymal stem cells (MSCs). Recent studies indicated that hAMCs had immunosuppressive functions and might be used in treatment of some autoimmune diseases. The aim of this study is to explore the feasibility of using hAMCs for treatment rats with collagen-induced arthritis (CIA), a classic animal model for human rheumatoid arthritis.

METHODS

SD rats were immunised with type II collagen and Freund's incomplete adjuvant. hAMCs were injected intraperitoneal when arthritis had become established. The arthritis was evaluated macroscopically and microscopically. Serum levels of IFN-γ, TNF-α, SOD, MDA, GSH-Px and T-AOC were detected by commercially assay kits. CD4⁺/CD8⁺ T-cell ratio in peripheral blood was examined by flow cytometry. Proliferation of splenocytes was evaluated using MTT assay.

RESULTS

The results demonstrated that application of hAMCs significantly ameliorated severity of arthritis and decreased the histopathological changes in CIA rats. Consistently, production of proinflammatory cytokines such as IFN-γ and TNF-α was dramatically inhibited. Moreover, hAMCs exerted anti-oxidative capacity by significantly raising the levels of SOD, GSH-Px, T-AOC and lowering the level of MDA. In addition, hAMCs also remarkably restored CD4⁺/CD8⁺ T-cell ratio and induced hyporesponsiveness of T lymphocytes by inhibiting their active proliferation. Finally, hAMCs had no obvious side effect on CIA rats.

CONCLUSIONS

In conclusion, our results indicated that hAMCs could attenuate the disease development in rats with CIA, which might be a promising cell source for therapy of rheumatoid arthritis.

摘要

目的

人羊膜间充质细胞(hAMCs)是从人胎盘羊膜中分离出来的一类独特的间充质干细胞(MSCs)。最近的研究表明,hAMCs具有免疫抑制功能,可能用于治疗某些自身免疫性疾病。本研究的目的是探讨使用hAMCs治疗胶原诱导性关节炎(CIA)大鼠的可行性,CIA是人类类风湿性关节炎的经典动物模型。

方法

用II型胶原和弗氏不完全佐剂免疫SD大鼠。当关节炎形成后,腹腔注射hAMCs。通过宏观和微观评估关节炎情况。使用商业检测试剂盒检测血清中IFN-γ、TNF-α、SOD、MDA、GSH-Px和T-AOC的水平。通过流式细胞术检测外周血中CD4⁺/CD8⁺ T细胞比例。使用MTT法评估脾细胞的增殖情况。

结果

结果表明,应用hAMCs可显著改善CIA大鼠的关节炎严重程度,并减少组织病理学变化。同样,促炎细胞因子如IFN-γ和TNF-α的产生受到显著抑制。此外,hAMCs通过显著提高SOD、GSH-Px、T-AOC水平并降低MDA水平发挥抗氧化能力。另外,hAMCs还显著恢复了CD4⁺/CD8⁺ T细胞比例,并通过抑制T淋巴细胞的活跃增殖诱导其低反应性。最后,hAMCs对CIA大鼠没有明显的副作用。

结论

总之,我们的结果表明,hAMCs可以减轻CIA大鼠的疾病发展,这可能是类风湿性关节炎治疗中一种有前景的细胞来源。

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