Intramyocardial delivery of mesenchymal stem cells 3 days after myocardial infarction increased resting myocardial blood flow over the first week compared with placebo (0.17 vs 0.09; P<0.01).
Does intramyocardial injection of allogeneic mesenchymal stem cells improve myocardial blood flow and LV function in a porcine model of myocardial infarction?
In a porcine model of MI, early intramyocardial delivery of MSCs increases tissue perfusion, which precedes improvements in LV function and reductions in apoptosis.
Absolute Event Rate: 0.17% vs 0.09%
p-value: p=<0.01
The underlying mechanism(s) of improved left ventricular function (LV) due to mesenchymal stem cell (MSC) administration after myocardial infarction (MI) remains highly controversial. Myocardial regeneration and neovascularization, which leads to increased tissue perfusion, are proposed mechanisms. Here we demonstrate that delivery of MSCs 3 days after MI increased tissue perfusion in a manner that preceded improved LV function in a porcine model. MI was induced in pigs by 60-min occlusion of the left anterior descending coronary artery, followed by reperfusion. Pigs were assigned to receive intramyocardial injection of allogeneic MSCs (200 million, approximately 15 injections) (n = 10), placebo (n = 6), or no intervention (n = 8). Resting myocardial blood flow (MBF) was serially assessed by first-pass perfusion magnetic resonance imaging (MRI) over an 8-wk period. Over the first week, resting MBF in the infarct area of MSC-treated pigs increased compared with placebo-injected and untreated animals 0.17 +/- 0.03, 0.09 +/- 0.01, and 0.08 +/- 0.01, respectively, signal intensity ratio of MI to left ventricular blood pool (LVBP); P < 0.01 vs. placebo, P < 0.01 vs. nontreated. In contrast, the signal intensity ratios of the three groups were indistinguishable at weeks 4 and 8. However, MSC-treated animals showed larger, more mature vessels and less apoptosis in the infarct zones and improved regional and global LV function at week 8. Together these findings suggest that an early increase in tissue perfusion precedes improvements in LV function and a reduction in apoptosis in MSC-treated hearts. Cardiac MRI-based measures of blood flow may be a useful tool to predict a successful myocardial regenerative process after MSC treatment.
Schuleri et al. (Sat,) conducted a other in Myocardial infarction (n=24). Allogeneic mesenchymal stem cells (MSCs) vs. Placebo or no intervention was evaluated on Resting myocardial blood flow (MBF) over the first week (signal intensity ratio of MI to left ventricular blood pool) (p=<0.01). Intramyocardial delivery of mesenchymal stem cells 3 days after myocardial infarction increased resting myocardial blood flow over the first week compared with placebo (0.17 vs 0.09; P<0.01).