title: Mesenchymal Stromal Cells Mitigate Experimental Colitis via Insulin-like Growth Factor Binding Protein 7-mediated Immunosuppression.
abstract: Mesenchymal stromal cells (MSCs) have shown great potential for treating inflammatory bowel disease, which is ameliorated through paracrine cross talk between MSCs and T-cells. Members of the insulin-like growth factor binding protein (IGFBP) family have important immunomodulatory functions in MSCs, but the underlying mechanisms behind these functions have not yet been clearly elucidated. In this study, we investigate whether MSC-produced IGFBP7 is involved in immune modulation using a mouse experimental colitis model. Gene expression profiling revealed that IGFBP7 was highly expressed in MSCs. Consistent with this findings, IGFBP7 knockdown in MSCs significantly decreased their immunomodulatory properties, decreasing the antiproliferative functions of MSCs against T-cells, while also having an effect on the proinflammatory cytokine production of the T-cells. Furthermore, in the mouse experimental colitis model, MSC-derived IGFBP7 ameliorated the clinical and histopathological severity of induced colonic inflammation and also restored the injured gastrointestinal mucosal tissues. In conclusion, IGFBP7 contributes significantly to MSC-mediated immune modulation, as is shown by the ability of IGFBP7 knockdown in MSCs to restore proliferation and cytokine production in T-cells. These results suggest that IGFBP7 may act as a novel MSC-secreted immunomodulatory factor.
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 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, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Department of Experimental Physiology, Zhongshan Medical School, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Lei
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Muyun
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wanwen
authors.initials: W
authors.lastname: Lin
authors.affiliation: Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Dongxi
authors.initials: D
authors.lastname: Hong
authors.affiliation: Department of Histopathology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tuo
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Mei Hua
authors.initials: MH
authors.lastname: Jiang
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Xia
authors.affiliation: The Cardiovascular Center, Gaozhou People's Hospital, Maoming, China.
authors.forename: Maosheng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 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, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 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, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Andy Peng
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D007155:Immunologic Factors / Q000378:metabolism*; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D015854:Up-Regulation
chemical_list: D007155:Immunologic Factors; D018969:Insulin-Like Growth Factor Binding Proteins; C102529:insulin-like growth factor binding protein-related protein 1