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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

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.

Original languageEnglish
Article number109
Pages (from-to)1-12
Number of pages12
JournalStem Cell Research and Therapy
Volume7
Issue number1
DOIs
StatePublished - 2016
Externally publishedYes

Funding

FundersFunder number
Fundamental Research Funds for the Central Universities of Sun Yat-sen University15ykpy12
Natural Fund of Guangdong Province2016A030310226
National Natural Science Foundation of China81301769, 81270473, 81470821
Guangdong Science and Technology Department2014A020212128, 2016A020214006
Pearl River S and T Nova Program of Guangzhou201610010126

    Keywords

    • B regulatory cell
    • Colitis
    • Crohn's disease
    • Mesenchymal stem cells
    • T helper cell

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