title: Allogeneic adipose stem cell therapy in acute myocardial infarction.
abstract: BACKGROUND
  Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing.
  
  
  METHODS
  Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated.
  
  
  RESULTS
  Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P < 0.01), T lymphocytes (1 ± 0.4 vs. 0.4 ± 0.3% of area CD3(+) ; P < 0.05) and expression of vascular endothelial growth factor (VEGF; 32 ± 7% vs. 20 ± 4% of area VEGF(+) ; P < 0.01). Allogeneic ATMSC-based therapy did not change ejection fraction but generated alloantibodies.
  
  
  CONCLUSIONS
  The present study is the first to demonstrate that allogeneic ATMSCs elicit an immune response and, when administered immediately after reperfusion, are more effective in increasing VEGF expression and neovascularization.
authors.affiliation: Department of Cardiology, Institut del Tòrax, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rigol
authors.forename: Núria
authors.initials: N
authors.lastname: Solanes
authors.forename: Santiago
authors.initials: S
authors.lastname: Roura
authors.forename: Mercè
authors.initials: M
authors.lastname: Roqué
authors.forename: Laura
authors.initials: L
authors.lastname: Novensà
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Dantas
authors.forename: Jaume
authors.initials: J
authors.lastname: Martorell
authors.forename: Marta
authors.initials: M
authors.lastname: Sitges
authors.forename: José
authors.initials: J
authors.lastname: Ramírez
authors.forename: Antoni
authors.initials: A
authors.lastname: Bayés-Genís
authors.forename: Magda
authors.initials: M
authors.lastname: Heras
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D004195:Disease Models, Animal; D006085:Graft Survival; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D018613:Microscopy, Confocal; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Adipose tissue-derived stem cells; allogeneic stem cells; experimental study; myocardial infarction; neovascularisation; time of administration