TY - JOUR
T1 - Human umbilical cord-derived mesenchymal stem cells protect against experimental colitis via CD5+ B regulatory cells
AU - Chao, Kang
AU - Zhang, Shenghong
AU - Qiu, Yun
AU - Chen, Xiaoyong
AU - Zhang, Xiaoran
AU - Cai, Chuang
AU - Peng, Yanwen
AU - Mao, Ren
AU - Pevsner-Fischer, Meirav
AU - Ben-Horin, Shomron
AU - Elinav, Eran
AU - Zeng, Zhirong
AU - Chen, Baili
AU - He, Yao
AU - Xiang, Andy Peng
AU - Chen, Minhu
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - B regulatory cell
KW - Colitis
KW - Crohn's disease
KW - Mesenchymal stem cells
KW - T helper cell
UR - http://www.scopus.com/inward/record.url?scp=84992135132&partnerID=8YFLogxK
U2 - 10.1186/s13287-016-0376-2
DO - 10.1186/s13287-016-0376-2
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C2 - 27515534
AN - SCOPUS:84992135132
SN - 1757-6512
VL - 7
SP - 1
EP - 12
JO - Stem Cell Research and Therapy
JF - Stem Cell Research and Therapy
IS - 1
M1 - 109
ER -