期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 6, 期 5, 页码 -出版社
WILEY
DOI: 10.1161/JAHA.117.005771
关键词
adipose tissue-derived mesenchymal stem cells; allogeneic origin; myocardial infarction; myocardial perfusion; vascular density
资金
- Fundacion la Marato de TV3 [122230]
- Fondo de Investigacion Sanitaria Instituto de Salud Carlos III
- Fondo Europeo de Desarrollo Regional [FIS PI14/01682, RD12/0042/0006, RD12/0042/0047, RD12/0019/0029, TerCel RD16/0011/0006]
- CIBER Cardiovascular project [CB16/11/00403]
- Ministerio de Educacion y Ciencia [SAF2011-30067-C02-01, SAF2014-59892]
- Ministerio de Economia, Industria, y Competitividad through the Instituto de Salud Carlos III (Rio Hortega fellowship)
- Fundacion Jesus Serra
- Fundacion Interhospitalaria de Investigacion Cardiovascular (FIC)
- CNIC (FICNIC fellowship)
- Medis Medical Imaging Systems BV
- CNIC
- Ministerio de Economia, Industria, y Competitividad (MINECO)
- Pro CNIC Foundation
- Severo Ochoa Center of Excellence (MINECO award) [SEV-2015-0505]
- la Caixa Banking Foundation
- Generalitat de Catalunya (SGR, CERCA Programme)
- ACCIO (Catalonia Trade Investment
- Generalitat de Catalunya) under the Catalonian ERDF operational program (European Regional Development Fund)
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.
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