title: Cyclophosphamide Combined with Bone Marrow Mesenchymal Stromal Cells Protects against Bleomycin-induced Lung Fibrosis in Mice.
abstract: BACKGROUND
  To examine the effects and possible mechanism of the immunosuppressant agent cyclophosphamide (CP) combined with bone marrow mesenchymal stromal cells (BM-MSCs) on bleomycin induced lung fibrosis in mice.
  
  
  METHODS
  BM-MSCs labeled with red fluorescence protein (RFP) from male Friend virus B-type(FVB) mice were cultured in vitro. Pulmonary fibrosis(PF) was induced in female wild type FVB mice and mice were randomly divided into five groups: control, model, CP, BM-MSCs, and BM-MSCs+CP. Pathological changes and distribution of RFP (+) BMSC in lung tissue were observed and hydroxyproline (Hyp) content in the lungs was measured. Changes in TGF-β mRNA, PDGF mRNA, and SDF-1mRNA expression in lung tissue were measured.
  
  
  RESULTS
  PF and Hyp levels in the BM-MSCs and BM-MSCs+CP groups were significantly alleviated (p<0.01) compared to the model group. The RFP (+) cells were distributed in the periphery of the alveolar space and endomembrane of bronchus. Hyp levels were reduced in the BM-MSCs+CP group compared to the BM-MSCs group (p<0.05). TGF-β and PDGF levels in the BM-MSCs and BM-MSCs+CP groups were higher than in the control or model group (p<0.05). SDF-1 level in the CP group showed no significant differences compared to the control group, in the other groups were higher than in the control group (p<0.05) and in the BM-MSCs+CP group was lower than in the BM-MSCs group (p<0.05).
  
  
  CONCLUSIONS
  It was concluded that CP alone does not improve PF and may be harmful. In contrast, combined application of BM-MSCs with CP provided better protection against PF and may serve as an effective therapy.
authors.affiliation: Department of Respiratory Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jiabo
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Department of cardiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Respiratory Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Respiratory Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China drliyanqin@126.com.
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001681:Biological Assay; D001761:Bleomycin; D002454:Cell Differentiation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control* / Q000628:therapy*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D001761:Bleomycin; D003520:Cyclophosphamide; D003094:Collagen; D006909:Hydroxyproline
keywords: bone marrow mesenchymal stromal cells (BM-MSCs); cyclophosphamide (CP); pulmonary fibrosis (PF); red fluorescence protein; stromal cell-derived factor (SDF-1)