title: Combinatorial Intervention with Mesenchymal Stem Cells and Granulocyte Colony-Stimulating Factor in a Rat Model of Ulcerative Colitis.
abstract: BACKGROUND
  Bone marrow mesenchymal stem cells sometimes improve symptoms of inflammatory bowel disease.
  
  
  OBJECTIVE
  To test the effects of combined granulocyte colony-stimulating factor (G-CSF) and MSC therapy in a rat model of ulcerative colitis (UC).
  
  
  METHODS
  Seventy-two rats with TNBS-induced UC were divided into control or treatment groups: control (no disease and no treatment), no treatment (model), 5-aminosalicylate (5-ASA) enema, or MSCs (labeled with BrdU) with (MSC/GCSF) or without (MSC) G-CSF, and G-CSF alone (GCSF). On days 14 and 28 post-treatment, macroscopic and histological appearances were assessed and the disease activity index (DAI) scored to evaluate the severity of disease. BrdU-labeled MSCs were identified by immunofluorescence to confirm transplantation and their location. The inflammatory profile of each group was evaluated by measuring expression of nuclear NF-κB p65, serum TNF-α, and IL-10 and by activity of mucosal myeloperoxidase (MPO).
  
  
  RESULTS
  Rats receiving MSC and G-CSF combination therapy had increased recruitment of MSCs to the colonic mucosa compared with rats receiving MSC transplantation alone. On day 28, the DAI, MPO activity, serum TNF-α and IL-10 levels, and NF-κB p65 expression in the combination therapy group were significantly lower compared to animals receiving no treatment, MSCs alone, or G-CSF alone (P < 0.05).
  
  
  CONCLUSIONS
  Intravenously transplanted MSCs migrate and distribute to the colon to effectively alleviate the symptoms of UC, while G-CSF enhances this effect via an anti-inflammatory effect and improvement in the pathologic features of UC. G-CSF may be a promising therapeutic regulator of MSCs that can improve therapeutic outcomes in patients with UC.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China.
authors.forename: YinHua
authors.initials: Y
authors.lastname: Tang
authors.forename: YingYing
authors.initials: Y
authors.lastname: Chen
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Song
authors.forename: YongGuo
authors.initials: Y
authors.lastname: Li
authors.forename: LiJun
authors.initials: L
authors.lastname: Shi
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000628:therapy*; D005786:Gene Expression Regulation; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D019804:Mesalamine / Q000627:therapeutic use; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051381:Rats; D012720:Severity of Illness Index; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid