Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5(+) B regulatory cells.

Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5(+) B regulatory cells.
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人脐带间充质干细胞通过 CD5( ) B 调节细胞预防实验性结肠炎

DOI:
10.1186/s13287-016-0376-2
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发表时间:
2016-08-11
影响因子:
7.5
通讯作者:
Chen M
Chen M
中科院分区:
医学2区
文献类型:
--
作者:
Chao K;Zhang S;Qiu Y;Chen X;Zhang X;Cai C;Peng Y;Mao R;Pevsner-Fischer M;Ben-Horin S;Elinav E;Zeng Z;Chen B;He Y;Xiang AP;Chen M

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目的:明确人脐带源性间充质干细胞(hUC-MSCs)治疗结肠炎的作用,探讨CD5+ B细胞在MSC治疗中的作用。采用三硝基苯磺酸(TNBS)致结肠炎小鼠模型。HUC-MSCs经腹膜转移。评估生存率、结肠炎症状、宏观和组织学评分。流式细胞术检测淋巴细胞中CD4+ T辅助细胞(Th)亚群和CD5+调节性B细胞(Bregs)。ELISA和Bio-plex检测细胞因子水平。分离CD5+ B细胞进行体外共培养和适应性转移。HUC-MSC治疗通过提高生存率、缓解症状、改善宏观和组织学评分来缓解tnbs诱导的结肠炎。标记hUC-MSCs位于结肠炎小鼠的炎症区域。hUC-MSC治疗后,调节性T细胞(Tregs)和CD5+ B细胞增加,Th1细胞、Th17细胞和几种促炎细胞因子减少。适应性转移后,CD5+ B细胞主要存在于腹腔灌洗液中,通过纠正Treg/Th1/Th17失衡改善tnbs诱导的结肠炎。CD5+ B细胞也抑制t细胞增殖并产生白细胞介素(IL)-10。HUC-MSCs通过增加CD5+ B细胞和产生il -10的CD5+ Bregs的数量,以及纠正Treg/Th17/Th1失衡,来预防实验性结肠炎。本文的在线版本(doi:10.1186/s13287-016-0376-2)包含补充材料,可供授权用户使用。
To clarify the effect of human umbilical cord-derived mesenchymal stem cell (hUC-MSCs) treatment on colitis and to explore the role of CD5+ B cells in MSC therapy. The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peritoneally. Survival rates, colitis symptoms, and macroscopic and histologic scores were evaluated. CD4+ T helper (Th) cell subgroups and CD5+ regulatory B cell (Bregs) in lymphocytes were quantitated by flow cytometry. Cytokine levels were detected by ELISA and Bio-plex. CD5+ B cells were isolated for in vitro co-culture and adaptive transfer. HUC-MSC treatment alleviated TNBS-induced colitis by increasing survival rates, relieving symptoms, and improving macroscopic and histologic scores. Labeled hUC-MSCs were located in the inflamed areas of colitis mice. Increases in regulatory T cells (Tregs) and CD5+ B cells and decreases in Th1 cells, Th17 cells, and several pro-inflammatory cytokines were observed with hUC-MSC treatment. After adaptive transfer, CD5+ B cells, which were located mainly in the peritoneal lavage fluid, improved TNBS-induced colitis by correcting Treg/Th1/Th17 imbalances. CD5+ B cells also inhibited T-cell proliferation and produced interleukin (IL)-10. HUC-MSCs protected against experimental colitis by boosting the numbers of CD5+ B cells and IL-10-producing CD5+ Bregs, and correcting Treg/Th17/Th1 imbalances. The online version of this article (doi:10.1186/s13287-016-0376-2) contains supplementary material, which is available to authorized users.