Introduction

Mesenchymal stem cells (MSCs) are promising therapeutic tools in regenerative medicine. In particularly adipose tissue derived MSC (AMSC) has powerful potential for the therapeutics of rheumatoid arthritis (RA) because these cells can control immune balance. RA systemically occurs autoimmune disease. Interestingly, IL-1 receptor antagonist deficient (IL-1ra^−/−) mice induce inflammation in joints like RA. In RA therapy, although AMSC improves the inflammation activity, it is little known to play roles of extracellular microvesicles (EV) for improvement of RA. To clarify the MSC-derived EVs are involved amelioration mechanisms for RA by themselves, we examined the functional effects of development for RA by AMSC-EVs.

Methods

We isolated AMSCs derived mice adipose tissue and purified EVs from the culture supernatant of AMSCs. To examine whether EVs can improve RA, we administrated EVs or AMSCs to IL-1ra knockout mice as RA model mice. We analyzed EVs-included factor by western blot methods and RA improvement effect by ELISA.

Results

In this study, we showed that the swellings of joints on mice in wild type AMSC and that in AMSC-EVs decreased than that in IL-1ra^−/− mice-AMSC-EVs and in none-treated. We detected IL-1ra expression in AMSC-EVs in wild type mice but not that in IL-1ra^−/− mice. Proinflammatory cytokine expression changes in mice showed in AMSCs and AMSC-EVs, but no apparent differences cytokine expressions were detected in IL-1ra^−/− mice.

Conclusions

In this study, we concluded that MSCs might improve RA by the transferring of factors such as IL-1ra, which are included their MSC derived- EVs.

中文翻译：

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源自脂肪组织的间充质干细胞的细胞外微泡具有改善小鼠类风湿性关节炎的潜在能力

介绍

间充质干细胞（MSCs）是再生医学中很有前途的治疗工具。特别是脂肪组织来源的 MSC (AMSC) 具有治疗类风湿性关节炎 (RA) 的强大潜力，因为这些细胞可以控制免疫平衡。RA全身性地发生自身免疫性疾病。有趣的是，IL-1 受体拮抗剂缺陷型 (IL-1ra ^-/- ) 小鼠会在 RA 等关节中诱发炎症。在 RA 治疗中，虽然 AMSC 改善了炎症活性，但鲜为人知的是，细胞外微泡 (EV) 在改善 RA 方面发挥的作用还鲜为人知。为了阐明 MSC 衍生的 EV 本身涉及 RA 的改善机制，我们检查了 AMSC-EV 对 RA 发育的功能影响。

方法

我们从 AMSCs 的培养上清液中分离出 AMSCs 衍生的小鼠脂肪组织和纯化的 EV。为了检查 EVs 是否可以改善 RA，我们将 EVs 或 AMSCs 给予 IL-1ra 敲除小鼠作为 RA 模型小鼠。我们通过蛋白质印迹法分析了包含 EVs 的因子，并通过 ELISA 分析了 RA 改善效果。

结果

在这项研究中，我们发现野生型 AMSC 和 AMSC-EV 小鼠的关节肿胀比 IL-1ra ^-/-小鼠-AMSC-EV 和未处理小鼠的关节肿胀减少。我们在野生型小鼠的 AMSC-EVs 中检测到 IL-1ra 表达，但在 IL-1ra ^-/-小鼠中没有检测到。在 AMSCs 和 AMSC-EVs 中显示了小鼠的促炎细胞因子表达变化，但在 IL-1ra ^-/-小鼠中未检测到明显的细胞因子表达差异。

结论

在这项研究中，我们得出结论，MSCs 可能通过转移 IL-1ra 等因子来改善 RA，这些因子包括它们的 MSC 衍生的 EV。