Chao Kang, Zhang Shenghong, Qiu Yun, Chen Xiaoyong, Zhang Xiaoran, Cai Chuang, Peng Yanwen, Mao Ren, Pevsner-Fischer Meirav, Ben-Horin Shomron, Elinav Eran, Zeng Zhirong, Chen Baili, He Yao, Xiang Andy Peng, Chen Minhu
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China.
Division of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, People's Republic of China.
Stem Cell Res Ther. 2016 Aug 11;7(1):109. doi: 10.1186/s13287-016-0376-2.
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.
阐明人脐带间充质干细胞（hUC-MSCs）治疗对结肠炎的影响，并探讨CD5(+) B细胞在间充质干细胞治疗中的作用。
采用三硝基苯磺酸（TNBS）诱导的结肠炎小鼠模型。经腹膜注射hUC-MSCs。评估生存率、结肠炎症状以及大体和组织学评分。通过流式细胞术对淋巴细胞中的CD4(+)辅助性T（Th）细胞亚群和CD5(+)调节性B细胞（Bregs）进行定量分析。采用酶联免疫吸附测定（ELISA）和生物芯片技术检测细胞因子水平。分离CD5(+) B细胞进行体外共培养和适应性转移。
hUC-MSCs治疗通过提高生存率、缓解症状以及改善大体和组织学评分，减轻了TNBS诱导的结肠炎。标记的hUC-MSCs定位于结肠炎小鼠的炎症区域。hUC-MSCs治疗后观察到调节性T细胞（Tregs）和CD5(+) B细胞增加，Th1细胞、Th17细胞以及几种促炎细胞因子减少。适应性转移后，主要位于腹腔灌洗液中的CD5(+) B细胞通过纠正Treg/Th1/Th17失衡改善了TNBS诱导的结肠炎。CD5(+) B细胞还抑制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数量以及纠正Treg/Th17/Th1失衡，对实验性结肠炎起到保护作用。
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