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

Abstract Background 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. Methods The trinitrobenzenesulfonic acid (TNBS)-induced colitis mouse model was used. HUC-MSCs were transferred peri...

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Main Authors: Kang Chao, Shenghong Zhang, Yun Qiu, Xiaoyong Chen, Xiaoran Zhang, Chuang Cai, Yanwen Peng, Ren Mao, Meirav Pevsner-Fischer, Shomron Ben-horin, Eran Elinav, Zhirong Zeng, Baili Chen, Yao He, Andy Peng Xiang, Minhu Chen
Format: Article
Language:English
Published: BMC 2016-08-01
Series:Stem Cell Research & Therapy
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Online Access:http://link.springer.com/article/10.1186/s13287-016-0376-2
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Summary:Abstract Background 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. Methods 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. Results 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. Conclusions 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.
ISSN:1757-6512