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BackgroundAutologous 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 ResultsThirty‐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‐1α 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.ConclusionsIn 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.

The authors thank Gonzalo J. López for the high-quality cardiac magnetic resonance examinations. Tamara Córdoba, Oscar Sanz, Nuria Valladares, Eugenio Fernández and the rest of the staff working in the animal facilities and CNIC ś farm were outstanding in animal care and unconditional collaboration. Laura García, Alberto Barroso and Xavier Navarro provided us with the ablation clamps and catheters and assisted us during the denervation procedures. Paula Garcia-Lunar provided valuable support with tissue sampling when it was most needed. SOURCES OF FUNDING:This work has been partially funded by the grant "Translational research project from the Sociedad Española de Cardiología" (to Dr. García-Álvarez) and by an unrestricted grant from Medtronic. The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).IDIBAPS belongs to the CERCA Programme and receives partial funding from the Generalitat de Catalunya.