title: Mesenchymal stem cells-regulated Treg cells suppress colitis-associated colorectal cancer.
abstract: BACKGROUND
  Previous studies have produced controversial results regarding whether mesenchymal stem cells (MSCs) promote or inhibit tumor development. Given the dual role of MSCs in inflammation and cancer, in this study the colitis-associated colorectal cancer (CAC) model was used to examine whether umbilical cord tissue-derived MSCs could prevent neoplasm by inhibiting chronic inflammation.
  
  
  METHODS
  MSCs were obtained and identified using flow cytometry. Colitis-associated colorectal cancer model was induced using azoxymethane (AOM) and dextran sulfate sodium (DSS) and MSCs were injected intravenously twice. Levels of immune cells in mesenteric lymph node including regulatory T (Treg) cells were detected using flow cytometry. Naïve T cells and Jurkat cells were co-cultured with MSCs and the effect of MSCs on Treg cells differentiation was evaluated.
  
  
  RESULTS
  After injection through tail vein, MSCs could migrate to colon and suppress colitis-related neoplasm. This tumor suppressive effect was characterized by longer colon length, decreased tumor numbers and decreased expression of Ki-67. Moreover, MSCs alleviated the pathology of inflammation in the colitis stage of CAC model and inhibited inflammation cytokines both in colon and serum. Furthermore, Treg cells were accumulated in mesenteric lymph node of MSCs-treated mice while the percentage of T helper cells 2 (Th2) and Th17 were not changed. Of note, MSCs secreted transforming growth factor-β (TGF-β) enhanced the induction of Treg cells from naïve T cells. The conditioned medium of MSCs also activated Smad2 signaling, which has been reported to regulate Treg cells.
  
  
  CONCLUSIONS
  These results proved that MSCs could migrate to colon tissues and induce the differentiation of Treg cells via Smad2 as so to inhibit the colitis and suppress the development of CAC.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. trjtrjtrj@163.com.
authors.forename: Rui-jing
authors.initials: RJ
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. shensn@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China. shensn@nju.edu.cn.
authors.forename: Su-nan
authors.initials: SN
authors.lastname: Shen
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. 23546057@qq.com.
authors.forename: Xiao-yin
authors.initials: XY
authors.lastname: Zhao
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. 367081746@qq.com.
authors.forename: Yun-zhong
authors.initials: YZ
authors.lastname: Nie
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. xuyujun11@126.com.
authors.forename: Yu-jun
authors.initials: YJ
authors.lastname: Xu
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. 1124438023@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. jinanmingming@126.com.
authors.forename: Ming-ming
authors.initials: MM
authors.lastname: Lv
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. yayihou@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China. yayihou@nju.edu.cn.
authors.forename: Ya-yi
authors.initials: YY
authors.lastname: Hou
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, China. wangtt@nju.edu.cn.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China. wangtt@nju.edu.cn.
authors.forename: Ting-ting
authors.initials: TT
authors.lastname: Wang
mesh_terms: D000818:Animals; D001397:Azoxymethane; D018791:CD4 Lymphocyte Count; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D003106:Colon / Q000166:cytology / Q000276:immunology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000097:blood; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D016207:Cytokines; D051899:Smad2 Protein; D016264:Dextran Sulfate; D001397:Azoxymethane