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
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13287-016-0376-2
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author 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
author_facet 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
author_sort Kang Chao
collection DOAJ
description 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.
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spelling doaj.art-cb5814e152fd4b44af79fba27a72780f2022-12-22T03:16:51ZengBMCStem Cell Research & Therapy1757-65122016-08-017111210.1186/s13287-016-0376-2Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cellsKang Chao0Shenghong Zhang1Yun Qiu2Xiaoyong Chen3Xiaoran Zhang4Chuang Cai5Yanwen Peng6Ren Mao7Meirav Pevsner-Fischer8Shomron Ben-horin9Eran Elinav10Zhirong Zeng11Baili Chen12Yao He13Andy Peng Xiang14Minhu Chen15Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityCenter for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen UniversityCenter for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen UniversityCenter for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen UniversityCenter for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Immunology, Weizmann Institute of ScienceDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDepartment of Immunology, Weizmann Institute of ScienceDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityCenter for Stem Cell Biology and Tissue Engineering, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen UniversityDivision of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen UniversityAbstract 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.http://link.springer.com/article/10.1186/s13287-016-0376-2Mesenchymal stem cellsColitisCrohn’s diseaseB regulatory cellT helper cell
spellingShingle 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
Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
Stem Cell Research & Therapy
Mesenchymal stem cells
Colitis
Crohn’s disease
B regulatory cell
T helper cell
title Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
title_full Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
title_fullStr Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
title_full_unstemmed Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
title_short Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
title_sort human umbilical cord derived mesenchymal stem cells protect against experimental colitis via cd5 b regulatory cells
topic Mesenchymal stem cells
Colitis
Crohn’s disease
B regulatory cell
T helper cell
url http://link.springer.com/article/10.1186/s13287-016-0376-2
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