Abstract 16881: Intracoronary Delivery of Allogeneic Mesenchymal Precursor Cells Directly after Acute Myocardial Infarction Improves Cardiac Function and Myocardial Perfusion and Decreases Adverse Left Ventricular Remodeling in Sheep
Rationale Mesenchymal precursor cells (MPC) hold great promise for the treatment of cardiovascular disease. These multipotent cells produce a vast array of angiotrophic factors and immune-modulatory cytokines. Moreover, they are immune privileged and can be given in an allogeneic setting. The aim of the current study is to investigate the efficacy and find the optimal dose of intracoronary MPC transplantation in a large animal model of AMI.
Methods and Results: 30 female sheep subjected to an anterior AMI by mid LAD occlusion were randomized to receive either saline (n=10), 12.5 (n=7), 25.0 (n=7) or 37.5 (n=6) x10(6) allogeneic MPC by intracoronary infusion directly post AMI. Left ventricular function was assessed using PV loop analysis at baseline and 8 weeks FU, followed by sacrifice and tissue processing for (immune)histological analyses. Global LVEF in control animals deteriorated to 42.5 ± 3.6% and was improved in MPC treated animals by 11,9% to 54.4 ± 1.1% (rel. change + 22%, P<0.001). LV adverse remodelling was abrogated by MPC therapy, resulting in a marked difference in end systolic volumes (Co (n=10): 98.6 ± 5.1 mL vs. MPC (n=20): 66 ± 1.0 mL, P<0.001). In accordance to this, collagen content was reduced by more than 50% in both border and remote areas of MPC treated animals (P<0.005). End-systolic elastance, a PV loop derived, load independent parameter of contractile function, was enhanced by 49% in the MPC treated group from 0.88 ± 0.05 to 1.31 ± 0.08 as compared to the control group (P=0.022). Histological analysis showed that functional improvement was associated with a 69% increase in capillary density in the infarct border zone (Co: 1196 ± 87 vs. 2019 ± 119 capillaries per mm2, P< 0.001), as well as a 122% increase in arterioles in the infarct area (Co: 21.7 ± 4.0 vs. 48.1 ± 4.2 arterioles per FOV, P<0.001), suggestive of increased perfusion. In the current study, a dose-effect association was demonstrated on the histological end points including neo-capillary formation and reduction of myocardial fibrosis.
Conclusion: We are the first to show that intracoronary infusion of allogeneic MPC is safe and feasible in AMI. MPC infusion leads to preserved left ventricular systolic function, reduced LV remodelling and increased neo-capillary and arteriolar formation.
- Regenerative medicine stem cells
- Myocardial infarction
- Percutaneous coronary intervention
- Pressure – volume relation
- © 2010 by American Heart Association, Inc.