Intracoronary administration of allogeneic adipose tissue-derived mesenchymal stem cells improves myocardial perfusion but not left ventricle function,in a translational model of acute myocardial infarction

Background- autologous adipose tissue-derived mesenchymal stem cells (atmscs) therapy is a promising strategy to improve post-myocardial infarction outcomes. in a porcine model of acute myocardial infarction,we studied the long-term effects and the mechanisms involved in allogeneic atmscs administration on myocardial performance. methods and results- thirty-eight pigs underwent 50 minutes of coronary occlusion; the study was completed in 33 pigs. after reperfusion,allogeneic atmscs or culture medium (vehicle) were intracoronarily administered. follow-ups were performed at short (2 days after acute myocardial infarction vehicle-treated,n=10; atmscs-treated,n=9) or long term (60 days after acute myocardial infarction vehicle-treated,n=7; atmscs-treated,n=7). at short term,infarcted myocardium analysis showed reduced apoptosis in the atmscs-treated animals (48.6±6% versus 55.9±5.7% in vehicle; p=0.017); enhancement of the reparative process with up-regulated vascular endothelial growth factor,granulocyte macrophage colony-stimulating factor,and stromal-derived factor-1a gene expression; and increased m2 macrophages (67.2±10% versus 54.7±10.2% in vehicle; p=0.016). in long-term groups,increase in myocardial perfusion at the anterior infarct border was observed both on day-7 and day-60 cardiac magnetic resonance studies in atmscs-treated animals,compared to vehicle (87.9±28.7 versus 57.4±17.7 ml/min per gram at 7 days; p=0.034 and 99±22.6 versus 43.3±14.7 22.6 ml/min per gram at 60 days; p=0.0001,respectively). at day 60,higher vascular density was detected at the border zone in the atmscs-treated animals (118±18 versus 92.4±24.3 vessels/mm2 in vehicle; p=0.045). cardiac magnetic resonance-measured left ventricular ejection fraction of left ventricular volumes was not different between groups at any time point. conclusions- in this porcine acute myocardial infarction model,allogeneic atmscs-based therapy was associated with increased cardioprotective and reparative mechanisms and with better cardiac magnetic resonance-measured perfusion. no effect on left ventricular volumes or ejection fraction was observed. © 2017 the authors.