title: Does pretreatment of bone marrow mesenchymal stem cells with 5-azacytidine or double intravenous infusion improve their therapeutic potential for dilated cardiomyopathy?
abstract: BACKGROUND
  This study was designed to investigate whether pretreatment of bone marrow mesenchymal stem cells (BMSCs) with 5-azacytidine (5-aza) or double intravenous infusion could enhance their therapeutic potential for dilated cardiomyopathy (DCM).
  
  
  METHODS
  BMSCs were cultured for 2 weeks in the presence or absence of 5-aza and DCM serum. The cultured BMSCs (Groups 1 and 2), 5-aza-induced BMSCs (Groups 3 and 4), and medium alone (model control) were transplanted into 80 female Wistar rats by intravenous tail vein injection. Double infusion of BMSCs with 1-day time-interval was carried out in Groups 2 and 4. Postmortem histological analysis and evaluation of heart function were performed at 4 weeks post-transplantation.
  
  
  RESULTS
  Some transplanted BMSCs engrafted into myocardial tissue and were positive for cardiac marker troponin T. The hearts containing transplanted BMSCs secreted a larger amount of vascular endothelial growth factor. Cardiac function parameters and serum level of brain natriuretic peptide (BNP) did not differ among Groups 1, 3, and the model control. As compared with model control, BMSC transplantation in Groups 2 and 4 significantly decreased the serum level of BNP and improved cardiac contractile function, as evidenced by reduced left ventricular end-diastolic and end-systolic diameter, elevated ejection fraction, and fractional shortening.
  
  
  CONCLUSIONS
  BMSC transplantation is a promising strategy for the treatment of DCM. Pretreatment of BMSCs with 5-aza and DCM serum does not enhance their therapeutic efficacy, and the double intravenous BMSC infusion method is superior to single infusion for preserving cardiac contractile function in a rat model of DCM.
authors: Department of Pediatric Cardiology, First Affiliated Hospital of Jilin University, Changchun, Jilin Province, China.
authors: Sirui
authors: S
authors: Yang
authors: Jinhua
authors: J
authors: Piao
authors: Lianhua
authors: L
authors: Jin
authors: Yan
authors: Y
authors: Zhou
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D054338:Cell Transdifferentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006334:Heart Function Tests; D007262:Infusions, Intravenous; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016019:Survival Analysis; D020107:Troponin T / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D020107:Troponin T; D042461:Vascular Endothelial Growth Factor A; D020097:Natriuretic Peptide, Brain; D003094:Collagen; D001973:Bromodeoxyuridine; D001374:Azacitidine