title: Hepatocyte growth factor enhances the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model.
abstract: OBJECTIVE
  Specific and effective therapy for prevention or reversal of bronchiolitis obliterans (BO) is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stromal cells (MSCs) on BO.
  
  
  METHODS
  A mouse model of experimental BO was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients, which were then administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using fluorescence-activated cell sorting (FACS) for lymphocyte immunophenotype of spleen, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (rt-PCR) for cytokine expression, and histopathological analysis for the transplanted trachea.
  
  
  RESULTS
  The histopathologic recovery of allograft tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGF-treated mice. Furthermore, the allo-transplantation-induced immunophenotype disorders of the spleen, including regulatory T (Treg), T helper (Th)1, Th2 and Th17, were attenuated in both cell-treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma (IFN-γ), and increased expression of anti-inflammatory cytokine interleukin (IL)-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor (TGF)-β.
  
  
  CONCLUSIONS
  Treatment of BO with HGF gene modified MSCs results in reduction of local inflammation and promotion in recovery of allograft trachea histopathology. These findings might provide an effective therapeutic strategy for BO.
authors: HeBei North University, Zhangjiakou, China; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Xiao-Pei
authors: XP
authors: Cao
authors: Department of Hematology, Air Force General Hospital, Beijing, China.
authors: Dong-Mei
authors: DM
authors: Han
authors: Department of Experimental Pathology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Li
authors: L
authors: Zhao
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Zi-Kuan
authors: ZK
authors: Guo
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Feng-Jun
authors: FJ
authors: Xiao
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Yi-Kun
authors: YK
authors: Zhang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Xiao-Yan
authors: XY
authors: Zhang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China.
authors: Li-Sheng
authors: LS
authors: Wang
authors: Department of Hematology, Air Force General Hospital, Beijing, China. Electronic address: wanghengxiang123@aliyun.com.
authors: Heng-Xiang
authors: HX
authors: Wang
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing, China. Electronic address: wanghua@bmi.ac.cn.
authors: Hua
authors: H
authors: Wang
mesh_terms: D000818:Animals; D001989:Bronchiolitis Obliterans / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D017228:Hepatocyte Growth Factor
keywords: Bronchiolitis obliterans; Hepatocyte growth factor; Th cells; Treg cells; Umbilical cord–derived mesenchymal stromal cells