title: Bone marrow mesenchymal stromal cells with CD47 high expression via the signal transducer and activators of transcription signaling pathway preventing myocardial fibrosis.
abstract: This study was initiated to investigate the efficacy of myocardial fibrosis intervention via signal transducer and activators of transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells (MSC) in which being over-expressed with the aid of bispecific antibody (BiAb) and ultrasound-mediated microbubbles (MB). BiAb was prepared and combined with isolated MSC with CD47 overexpression from male mice and trans-fused into female mice with isoproterenol-induced myocardial fibrosis via the tail vein, followed by MB. This study included five groups. Five weeks after treatment, expression levels of the sex-determining region of Y-chromosome (SRY), matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) in myocardium were detected by fluorescent quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of signal transducer and activators of transcription (STAT) 1 and STAT 3 was detected by Western blot.
  
  
  RESULTS
  The highest homing number of MSC was in the CD47 + MSC + BiAb + MB group, second highest in the CD47 + MSC + BiAb group, and lowest in MSC alone. Compared with the Control group, CD47 + MSC + BiAb + MB, CD47 + MSC + BiAb, CD47 + MSC and MSC groups had decreased levels of MMP-9, TIMP-1, STAT 1 and collagen deposition, and increased levels of STAT 3. Up regulated STAT 3 and down regulated TIMP-1 were significantly different in CD47 + MSC + BiAb + MB compared with CD47 + MSC or CD47 + MSC + BiAb.
  
  
  CONCLUSIONS
  CD47 can enhance the homing rate and repairing efficacy of MSC. MSC can improve MMP-TIMP expression in injured myocardium and interfere with myocardial fibrosis after homing, a mechanism that may be related to the STAT-mediated signaling pathway.
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Chen
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Xing-Sheng
authors.initials: XS
authors.lastname: Li
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Zhong-Ming
authors.initials: ZM
authors.lastname: Yuan
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Gui-Qiong
authors.initials: GQ
authors.lastname: Li
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Ke
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Wu
authors.affiliation: Department of Gerontology, The No. 2 Hospital Affiliated to Chongqing Medical University Chongqing 400010, China.
authors.forename: Shi-Lan
authors.initials: SL
authors.lastname: Luo
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation; D007545:Isoproterenol; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D017207:Rats, Sprague-Dawley; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051876:Sex-Determining Region Y Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D018033:Antibodies, Bispecific; D051928:CD47 Antigen; C584934:CD47 protein, rat; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat; C494081:Stat1 protein, rat; C494088:Stat3 protein, rat; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D003094:Collagen; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D007545:Isoproterenol
keywords: CD47; Myocardial fibrosis; mesenchymal stromal cells; signal transducer and activators of transcription