Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/5119
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
Bobi, Joaquim | Solanes, Nuria | Fernandez-Jimenez, Rodrigo CNIC | Galan-Arriola, Carlos CNIC | Dantas, Ana Paula | Fernandez-Friera, Leticia CNIC | Galvez-Monton, Carolina | Rigol-Monzo, Elisabet | Aguero, Jaume CNIC | Ramirez, Jose | Roque, Merce | Bayes-Genis, Antoni | Sanchez-Gonzalez, Javier CNIC | Garcia-Alvarez, Ana CNIC | Sabaté, Manel | Roura, Santiago | Ibanez, Borja CNIC | Rigol, Montserrat
J Am Heart Assoc. 2017; 6(5):e005771
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-1 alpha 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/mm(2) 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.
adipose tissue-derived mesenchymal stem cells | allogeneic origin | myocardial infarction | myocardial perfusion | vascular density | RANDOMIZED PHASE-1 TRIAL | CARDIAC-FUNCTION | ISCHEMIC CARDIOMYOPATHY | PROMOTE ANGIOGENESIS | PROGENITOR CELLS | HEART-FAILURE | PORCINE MODEL | DISEASE | THERAPY | ISCHEMIA/REPERFUSION
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