title: Gene delivery with IFN-γ-expression plasmids enhances the therapeutic effects of MSCs on DSS-induced mouse colitis.
abstract: OBJECTIVE
  Interferon-γ (IFN-γ) is known to enhance the immunosuppressive properties of mesenchymal stem cells (MSCs). The aim of this study was to determine whether gene modification with IFN-γ-expression plasmids could boost the therapeutic effects of MSCs on DSS-induced colitis.
  
  
  METHODS
  We first reconstructed pcDNA3.1-IFNγ plasmids, transfected them to human umbilical cord derived MSCs, and detected the basic characters of MSCs including immune phenotype, cell vitality, proliferation, apoptosis and cell cycle progression after transfection. Subsequently, we analyzed the inhibition effect of IFN-γ-MSCs on T cell proliferation in vitro. Finally, we induced colitis in female C57BL/6 mice by 3 % DSS treatment and evaluated the therapeutic efficacy of IFN-γ-MSCs on colitis.
  
  
  RESULTS
  Transfection with pcDNA3.1-IFNγ did not change the basic characters of MSCs. Interestingly, IFN-γ-MSCs showed more potent immunosuppressive effects on the proliferation of T cells compared to normal MSCs. Furthermore, systemic infusion with IFN-γ-MSCs more efficiently ameliorated DSS-induced mouse colitis including colitis-related ease of body weight, increase of colon length, decrease of disease activity index, and improvement of small intestine tissues structure. In addition, IFN-γ-MSCs increased the populations of Foxp3(+) Tregs and Th2 cells both in mesenteric lymph node and spleen, upregulated indoleamine 2, 3-dioxygenase expression, and suppressed inflammatory cytokine production in mouse colon.
  
  
  CONCLUSIONS
  Gene delivery with IFN-γ-expression plasmids enhanced the therapeutic effects of MSCs on DSS-induced mouse colitis. This study provides an effective therapeutic strategy of MSCs for inflammatory diseases.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, 210093, People's Republic of China.
authors.forename: Yueqiu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Song
authors.forename: Huishuang
authors.initials: H
authors.lastname: Miao
authors.forename: Yujun
authors.initials: Y
authors.lastname: Xu
authors.forename: Mingming
authors.initials: M
authors.lastname: Lv
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Yayi
authors.initials: Y
authors.lastname: Hou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000473:pathology; D016207:Cytokines / Q000235:genetics*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D008810:Mice, Inbred C57BL; D010957:Plasmids; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D016264:Dextran Sulfate