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

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 peritonea...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981968/
https://www.ncbi.nlm.nih.gov/pubmed/27515534
http://dx.doi.org/10.1186/s13287-016-0376-2
Descripción
Sumario: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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13287-016-0376-2) contains supplementary material, which is available to authorized users.