VEGF165-overexpressing mesenchymal stromal cells reduce infarct size and improve left ventricular function in a sheep model of myocardial infarction

LOCATELLI PAOLA; OLEA FERNANDA DANIELA; HNATIUK ANNA; DE LORENZI ANDREA; RAMIREZ RODRIGO; CERDÁ MIGUEL; LAGUENS RUBÉN; CROTTOGINI ALBERTO

Foz de Iguazú

Congreso; Congreso Panamericano de Fisiología; 2014

Sociedade Brasileira de Fisiología

Mesenchymal stromal cells (MSCs) have cardioprotective effects in acute myocardial infarction (AMI). On the other hand, we have shown that intramyocardial injection of a plasmid encoding human VEGF165 (pVEGF) in sheep with AMI reduces infarct size and improves left ventricular (LV) function. We thus hipothesized that MSCs overexpressing VEGF165 (MSCs-pVEGF) would limit infarct size and improve LV function more than non-modified MSCs or pVEGF alone. In sheep, an infarct size of approximately15% of the LV mass was induced. A week later sheep received 20 million MSCs-pVEGF, or 20 million allogeneic MSCs, or 3,8 mg pVEGF, or placebo (2 ml PBS) in the peri-infarct (n=8 per group). Four and 30 days after AMI sheep underwent magnetic resonance (MRI) to assess infarct size and echocardiography to assess LV function. In additional sheep, MSCs-VEGF myocardial retention was assessed at 7 and 30 days by detecting the SRY gene of male donor MSCs injected in female sheep. Infarct size decreased by 31% in MSCs-pVEGF (from 13±5% to 9±4% of LV mass, p