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人子宫内膜再生细胞减轻小鼠肾缺血再灌注损伤。

Human endometrial regenerative cells attenuate renal ischemia reperfusion injury in mice.

作者信息

Sun Peng, Liu Jian, Li Wenwen, Xu Xiaoxi, Gu Xiangying, Li HongYue, Han Hongqiu, Du Caigan, Wang Hao

机构信息

Department of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

Tianjin General Surgery Institute, Tianjin, China.

出版信息

J Transl Med. 2016 Jan 28;14:28. doi: 10.1186/s12967-016-0782-3.

DOI:10.1186/s12967-016-0782-3
PMID:26822150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4730626/
Abstract

BACKGROUND

Endometrial regenerative cells (ERCs) is an attractive novel type of adult mesenchymal stem cells that can be non-invasively obtained from menstrual blood and are easily replicated at a large scale without tumorigenesis. We have previously reported that ERCs exhibit unique immunoregulatory properties in experimental studies in vitro and in vivo. In this study, the protective effects of ERCs on renal ischemia-reperfusion injury (IRI) were examined.

METHODS

Renal IRI in C57BL/6 mice was induced by clipping bilateral renal pedicles for 30 min, followed by reperfusion for 48 h. ERCs were isolated from healthy female menstrual blood, and were injected (1 million/mouse, i.v.) into mice 2 h prior to IRI induction. Renal function, pathological and immunohistological changes, cell populations and cytokine profiles were evaluated after 48 h of renal reperfusion.

RESULTS

Here, we showed that as compared to untreated controls, administration of ERCs effectively prevented renal damage after IRI, indicated by better renal function and less pathological changes, which were associated with increased serum levels of IL-4, but decreased levels of TNF-α, IFN-γ and IL-6. Also, ERC-treated mice displayed significantly less splenic and renal CD4(+) and CD8(+) T cell populations, while the percentage of splenic CD4(+)CD25(+) regulatory T cells and infiltrating M2 macrophages in the kidneys were significantly increased in ERC-treated mice.

CONCLUSIONS

This study demonstrates that the novel anti-inflammatory and immunoregulatory effects of ERCs are associated with attenuation of renal IRI, suggesting that the unique features of ERCs may make them a promising candidate for cell therapies in the treatment of ischemic acute kidney injury in patients.

摘要

背景

子宫内膜再生细胞(ERCs)是一种引人关注的新型成体间充质干细胞,可从月经血中无创获取,且易于大规模复制而不发生肿瘤形成。我们之前曾报道,在体外和体内实验研究中,ERCs表现出独特的免疫调节特性。在本研究中,我们检测了ERCs对肾缺血再灌注损伤(IRI)的保护作用。

方法

通过夹闭双侧肾蒂30分钟诱导C57BL/6小鼠发生肾IRI,随后再灌注48小时。从健康女性月经血中分离出ERCs,并在诱导IRI前2小时将其(100万个/小鼠,静脉注射)注入小鼠体内。肾再灌注48小时后评估肾功能、病理和免疫组织学变化、细胞群体及细胞因子谱。

结果

在此,我们表明,与未处理的对照组相比,给予ERCs可有效预防IRI后的肾损伤,表现为肾功能更好且病理变化更少,这与血清中IL-4水平升高,但TNF-α、IFN-γ和IL-6水平降低有关。此外,接受ERCs治疗的小鼠脾脏和肾脏中的CD4(+)和CD8(+) T细胞群体显著减少,而脾脏CD4(+)CD25(+)调节性T细胞的百分比以及肾脏中浸润的M2巨噬细胞在接受ERCs治疗的小鼠中显著增加。

结论

本研究表明,ERCs的新型抗炎和免疫调节作用与减轻肾IRI相关,提示ERCs的独特特性可能使其成为治疗患者缺血性急性肾损伤的细胞治疗的有希望的候选者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/f22e3f5a118a/12967_2016_782_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/0f31859d12aa/12967_2016_782_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/612a7ffb6c9a/12967_2016_782_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/06858a3868bd/12967_2016_782_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/8f4237956efe/12967_2016_782_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/ba61abc86556/12967_2016_782_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/2b3abceecfdb/12967_2016_782_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/f22e3f5a118a/12967_2016_782_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/0f31859d12aa/12967_2016_782_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/612a7ffb6c9a/12967_2016_782_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/06858a3868bd/12967_2016_782_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/8f4237956efe/12967_2016_782_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/ba61abc86556/12967_2016_782_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/2b3abceecfdb/12967_2016_782_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e7f/4730626/f22e3f5a118a/12967_2016_782_Fig7_HTML.jpg

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J Transl Med. 2014 Dec 5;12:344. doi: 10.1186/s12967-014-0344-5.
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Protective effect of CD4(+)CD25(high)CD127(low) regulatory T cells in renal ischemia-reperfusion injury.CD4(+)CD25(high)CD127(low)调节性 T 细胞对肾缺血再灌注损伤的保护作用。
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