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子宫内膜再生细胞通过调节小鼠 B 淋巴细胞治疗实验性结肠炎。

Treatment of experimental colitis by endometrial regenerative cells through regulation of B lymphocytes in mice.

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

Stem Cell Res Ther. 2018 May 22;9(1):146. doi: 10.1186/s13287-018-0874-5.

DOI:10.1186/s13287-018-0874-5
PMID:29784012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5963178/
Abstract

BACKGROUND

Endometrial regenerative cells (ERCs), a novel type of mesenchymal-like stem cell derived from menstrual blood, have been recently evaluated as an attractive candidate source in ulcerative colitis (UC); however, the mechanism is not fully understood. The present study was designed to investigate the effects of ERCs, especially on B-cell responses in UC.

METHODS

In this study, colitis was induced by administering 3% dextran sodium sulfate (DSS) via free drinking water for 7 days to BALB/c mice. In the treated group, mice were injected intravenously with 1 × 10 ERCs on days 2, 5, and 8 after DSS induction. Therapeutic effects were assessed by monitoring body weight, disease activity, and pathological changes. Subpopulations of lymphocytes were determined by flow cytometry. IgG deposition in the colon was examined by immunohistochemistry staining. Cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA), Western blot, or polymerase chain reaction (PCR) analysis. Adoptive transfer of regulatory B cells (Bregs) into colitis mice was performed.

RESULTS

Here, we demonstrated that ERC treatment prolonged the survival of colitis mice and attenuated disease activity with fewer pathological changes in colon tissue. ERCs decreased the proportion of immature plasma cells in the spleen and IgG deposition in the colon. On the other hand, ERCs increased the production of Bregs and the interleukin (IL)-10 level. Additionally, adoptive transferred Bregs exhibited significant therapeutic effects on colitis mice.

CONCLUSIONS

In conclusion, our results unravel the therapeutic role of ERCs on experimental colitis through regulating the B-lymphocyte responses.

摘要

背景

子宫内膜再生细胞(ERCs)是一种新型的间充质样干细胞,来源于月经血,最近被评估为溃疡性结肠炎(UC)有吸引力的候选来源;然而,其机制尚未完全阐明。本研究旨在探讨 ERCs 的作用,特别是对 UC 中 B 细胞反应的影响。

方法

在这项研究中,通过自由饮用 3%葡聚糖硫酸钠(DSS)诱导结肠炎,连续 7 天。在治疗组中,在 DSS 诱导后第 2、5 和 8 天,通过静脉注射 1×10 ERCs。通过监测体重、疾病活动度和病理变化来评估治疗效果。通过流式细胞术测定淋巴细胞亚群。通过免疫组织化学染色检测 IgG 在结肠中的沉积。通过酶联免疫吸附试验(ELISA)、Western blot 或聚合酶链反应(PCR)分析测定细胞因子水平。将调节性 B 细胞(Bregs)过继转移到结肠炎小鼠中。

结果

在这里,我们证明了 ERC 治疗可以延长结肠炎小鼠的存活时间,减轻疾病活动度,减少结肠组织的病理变化。ERC 减少了脾脏中未成熟浆细胞的比例和 IgG 在结肠中的沉积。另一方面,ERC 增加了 Bregs 的产生和白细胞介素(IL)-10 水平。此外,过继转移的 Bregs 对结肠炎小鼠表现出显著的治疗效果。

结论

总之,我们的结果揭示了 ERC 通过调节 B 淋巴细胞反应对实验性结肠炎的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/af6532982df9/13287_2018_874_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/719cae8edc5b/13287_2018_874_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/133b7d875a25/13287_2018_874_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/85608d23c631/13287_2018_874_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/00fa3722110c/13287_2018_874_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/1fee644872e5/13287_2018_874_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/af6532982df9/13287_2018_874_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/719cae8edc5b/13287_2018_874_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/133b7d875a25/13287_2018_874_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/85608d23c631/13287_2018_874_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/00fa3722110c/13287_2018_874_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/1fee644872e5/13287_2018_874_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4357/5963178/af6532982df9/13287_2018_874_Fig6_HTML.jpg

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