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源自脂肪组织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。

Extracellular microvesicles that originated adipose tissue derived mesenchymal stem cells have the potential ability to improve rheumatoid arthritis on mice.

作者信息

Tsujimaru Koichiro, Takanashi Masakatsu, Sudo Katsuko, Ishikawa Akio, Mineo Shoichiro, Ueda Shinobu, Kumagai Katsuyoshi, Kuroda Masahiko

机构信息

Department of Molecular Pathology, Tokyo Medical University, Japan.

Preclinical Research Center, Tokyo Medical University, 6-1-1, Shinjuku, Shinjuku-ku, Tokyo, 160-8402, Japan.

出版信息

Regen Ther. 2020 Dec 9;15:305-311. doi: 10.1016/j.reth.2020.08.004. eCollection 2020 Dec.

Abstract

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.

摘要

引言

间充质干细胞(MSCs)是再生医学中很有前景的治疗工具。特别是脂肪组织来源的间充质干细胞(AMSCs)在类风湿性关节炎(RA)治疗方面具有强大潜力,因为这些细胞可以控制免疫平衡。RA是一种全身性自身免疫疾病。有趣的是,白细胞介素-1受体拮抗剂缺陷(IL-1ra)小鼠会像RA一样引发关节炎症。在RA治疗中,虽然AMSCs可改善炎症活动,但关于其细胞外微泡(EVs)在改善RA方面所起的作用却知之甚少。为了阐明MSCs来源的EVs自身参与RA改善机制,我们研究了AMSC-EVs对RA发展的功能影响。

方法

我们从小鼠脂肪组织中分离出AMSCs,并从AMSCs的培养上清液中纯化出EVs。为了检测EVs是否能改善RA,我们将EVs或AMSCs给予作为RA模型小鼠的IL-1ra基因敲除小鼠。我们通过蛋白质印迹法分析了EVs所含因子,并通过酶联免疫吸附测定法分析了RA改善效果。

结果

在本研究中,我们发现野生型AMSC组小鼠和AMSC-EVs组小鼠的关节肿胀程度低于IL-1ra小鼠-AMSC-EVs组和未处理组。我们在野生型小鼠的AMSC-EVs中检测到IL-1ra表达,而在IL-1ra小鼠中未检测到。小鼠体内促炎细胞因子表达变化在AMSCs和AMSC-EVs中均有显示,但在IL-1ra小鼠中未检测到明显的细胞因子表达差异。

结论

在本研究中,我们得出结论,MSCs可能通过传递诸如IL-1ra等包含在其来源的EVs中的因子来改善RA。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15cc/7770341/5caf08a6a4a1/gr1.jpg

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