title: Bone marrow mesenchymal stromal cells with support of bispecific antibody and ultrasound-mediated microbubbles prevent myocardial fibrosis via the signal transducer and activators of transcription signaling pathway.
abstract: OBJECTIVE
  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) with the aid of bispecific antibody (BiAb) and ultrasound-mediated microbubbles (MB).
  
  
  METHODS
  BiAb (anti-CD29 × anti-myosin light chain antibody; AMLCA) was prepared and combined with isolated MSC from male mice and transfused into female mice with isoproterenol-induced myocardial fibrosis via the tail vein, followed by MB (MSC + BiAb + MB). This study included seven groups: MSC + BiAb + MB; MSC; BiAb; MB; MSC + BiAb; untreated; and control. 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). Collagen distribution was observed using Sirius Red staining. The protein expression of signal transducer and activators of transcription (STAT)1 and STAT3 was detected by Western blot.
  
  
  RESULTS
  The highest homing number of MSC was in the MSC + BiAb + MB group, second highest in the MSC + BiAb group, and lowest in MSC alone. Compared with the untreated group, MSC + BiAb + MB, MSC + BiAb and MSC groups had decreased levels of MMP-9, TIMP-1, STAT1 and collagen deposition, and increased levels of STAT3. Upregulated STAT3 and downregulated TIMP-1 were significantly different in MSC + BiAb + MB compared with MSC alone or MSC + BiAb.
  
  
  CONCLUSIONS
  The homing rate and repairing efficacy of MSC improved with treatment utilizing a combination of BiAb and MB. 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: Gerontology Department of the No. 2 Hospital affiliated to Chongqing Medical University, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.forename: Qing-Wei
authors.initials: QW
authors.lastname: Chen
authors.forename: Xing-Sheng
authors.initials: XS
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.forename: Si-Qiang
authors.initials: SQ
authors.lastname: Niu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhou
authors.forename: Gui-Qiong
authors.initials: GQ
authors.lastname: Li
authors.forename: Da-Zhi
authors.initials: DZ
authors.lastname: Ke
authors.forename: Xian-Gang
authors.initials: XG
authors.lastname: Mo
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D009202:Cardiomyopathies / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000166:cytology*
chemical_list: D050791:STAT Transcription Factors