Abstract 734: Cell Tracking Following the Intramyocardial Injection of MSCs After Myocardial Infarction
Background: We have previously shown that in a pig model of acute myocardial infarction (MI), allogeneic MSCs delivered intramyocardially reduced the extent of necrotic myocardium and promoted the reappearance of contractile myocardium along the subendocardial surface of the MI. Treated animals had substantial increases in global and regional cardiac performance. Whether or not this beneficial effect involves MSC differentiation or stimulation of endogenous repair mechanisms remains controversial. Here we addressed this controversy by assessing the relative contributions of these different mechanisms.
Methods: MI was induced in female Yorkshire pigs by a 60-min occlusion of the LAD, followed by reperfusion. 3 days after MI, animals received intramyocardial injections of either male allogeneic porcine MSCs (2.0 × 108 cells) or placebo, and were sacrificed at day 1, day 10 and 8 weeks post injection of MSCs and myocardium was analyzed to determine cell retention rate and differentiation using Y chromosome fluorescent in-situ hybridization (FISH).
Results: FISH analyis of the endocardial surface of the MI scar revealed significant reduction in cell engraftment at 8 weeks (5±4.6 per unit area 24 hours after MSC injection (n=2) vs. 0.20±0.5 per unit area at 8 weeks (n=6), P<0.002). Although MSC persistence declined, there was a marked reduction in myocyte apoptosis as assessed by TUNEL assay (19.29±1.39 and 8.42±2.17 units, respectively, p<0.05 in MSC treated pigs). The number of Ki-67 positive cardiomyocytes per unit area was not significantly different between control and MSC treated animals at 8 weeks.
Conclusion: Despite reduction in the number of MSCs over 8 weeks, there is evidence of myocardial regeneration coupled with a marked attenuation in myocyte apoptosis in the subendocardial rim of the MI. Together these findings suggest that MSCs both activate endogenous repair mechanisms and promote survival of myocytes in the cell cycle.