Mesenchymal Stem Cells (MSCs) in the Treatment of Inflammatory Bowel Disease
New research suggests that mesenchymal stem cells (MSCs) can help in the treatment of inflammatory bowel disease.
Theranostics. 2019 Jun 24;9(16):4633-4647. doi: 10.7150/thno.32260. eCollection 2019.Xiaoyong Chen,1,2,3,* Chuang Cai,2,* Dijing Xu,2,* Qiuli Liu,1 Shuwei Zheng,2 Longshan Liu,4 Gang Li,2Xiaoran Zhang,2 Xiaoping Li,2 Yuanchen Ma,2 Li Huang,2 Jieying Chen,2 Jiahao Shi,2 Xin Du,5Wenjie Xia,6,✉ Andy Peng Xiang,2,7,8,✉ and Yanwen Peng1,2
- The Biotherapy Center, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China.
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, 510080, China.
- Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
- Organ Transplant Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
- Hematological Department of Guangdong Province People’s Hospital, Guangzhou 510080, China.
- Institute of Blood Transfusion, Guangzhou Blood Centre, Guangzhou, 510095, China
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.
- Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 511436, China
Corresponding authors: Professor Andy Peng Xiang, Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University; Email: nc.ude.usys.liam@pgnaix or Professor Yanwen Peng, the Biotherapy Center, the Third Affiliated Hospital, Sun Yat-sen University, Email: nc.ude.usys.liam@wygnep or Dr Wenjie Xia, Institute of Blood Transfusion, Guangzhou Blood Centre, Email: moc.qq@158499793
*Authors contributed equally to this work.
Competing Interests: The authors have declared that no competing interest exists.
Rationale: Mesenchymal stem cells (MSCs) have been demonstrated to ameliorate inflammatory bowel disease by their actions on multiple immune cells, especially on regulatory B cells (Breg cells). However, the phenotypes and functions of human MSCs (hMSCs)-treated Breg cell subsets are not yet clear. Methods: Purified B cells were cocultured with MSCs and the phenotypes and immunomodulatory functions of the B cells were analyzed by FACS and proliferation assays in vitro. Also, a trinitrobenzenesulfonic acid-induced mouse colitis model was employed to detect the function of MSC-treated Breg cells in vivo. Results: We demonstrated that coculturing with hMSCs significantly enhanced the immunomodulatory activity of B cells by up-regulating IL-10 expression. We then identified that a novel regulatory B cellpopulation characterized by CD23 and CD43 phenotypic markers could be induced by hMSCs. The CD23+CD43+ Breg cells substantially inhibited the inflammatory cytokine secretion and proliferation of T cells through an IL-10-dependent pathway. More significantly, intraperitoneal injection of hMSCs ameliorated the clinical and histopathological severity in the mouse experimental colitis model, accompanied by an increase in the number of CD23+CD43+ Breg cells. The adoptive transfer of CD23+CD43+ B cells effectively alleviated murine colitis, as compared with the CD23-CD43- B cells. Treatment with CD23+CD43+ B cells, and not hMSCs, substantially improved the symptoms of colitis in B cell-depleted mice. Conclusion: the novel CD23+CD43+ Breg cell subset appears to be involved in the immunomodulatory function of hMSCs and sheds new light on elucidating the therapeutic mechanism of hMSCs for the treatment of inflammation-related diseases.