VEGF165-Overexpressing Mesenchymal Stromal Cells Reduce Infarct Size And Improve Left Ventricular Function In A Sheep Model Of Myocardial Infarction

LOCATELLI P ; OLEA FD; HNATIUK A; DE LORENZI A; RAMÍREZ R; CERDÁ M; LAGUENS R; CROTTOGINI A.

Foz Iguazu

Congreso; 1 St Panamerican Congress Of Physiological Sciences,; 2014

Sociedad Argentina 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 approximately 15% 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-pVEGF 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 MSCspVEGF (from 13±5% to 9±4% of LV mass, p