Abstract 15329: Allogeneic Mesenchymal Precursor Cells Preserve Cardiac Function Following Intracoronary Infusion in a Sheep Model of Acute Myocardial Infarction
Background Mesenchymal precursor cells (MPC) are cells that exerted cardio-protective, anti-remodeling, and pro-angiogenic actions in pre-clinical models of acute myocardial infarction (AMI). They are immune privileged and can be given in an allogeneic setting. In previous studies, MPC were delivered via endomyocardial or epicardial injections, whereas intracoronary infusion renders several advantages. The aim of the current large animal study was to assess the effect of intracoronary delivery of allogeneic MPC directly following an AMI.
Methods A total of 30 sheep, subjected to an anterior wall AMI, were blindly randomized to receive intracoronary infusion of allogeneic MPC (n=20) or saline (n=10) directly following the AMI. Cardiac function was assessed using echocardiography. After 8 weeks, sheep were sacrificed and the hearts excised for morphometric and histological analysis.
Results In the control group, global LVEF deteriorated to 36.6 ± 2.0%, whereas it was enhanced in treated sheep to 45.4 ± 1.4% (P= 0.009). Regional function improved, as fractional area change (FAC) in the apex increased by 39% in MPC-treated animals compared to controls (P= 0.027), and FAC in the mid-ventricle increased by 30% (P= 0.007). Systolic wall thickening in the antero-septal wall improved from 9.6 ± 5.5% in controls to 39.1 ± 1.8% in treated animals (P< 0.001) and in the anterior wall from 13.8 ± 3.6% to 34.7 ± 1.9% (P< 0.001). Morphometric analysis revealed that MPC treatment resulted in a 40% reduction in infarct size from 18.2 ± 1.7% of the LV infarcted in control animals to only 10.9 ± 0.6% in treated sheep (P< 0.001). Also, infarct thickness had improved in the treatment group (P< 0.001). Histological analysis showed an increase in blood vessel density of >50% in the infarct (P<0.001), remote (P=0.007) and border (P<0.001) areas evoked by MPC therapy. In addition, cardiomyocyte hypertrophy was reduced in border (P<0.001) and remote (P=0.002) areas, accompanied by reduced collagen contents, which is suggestive of decreased adverse remodeling.
Conclusion Intracoronary delivery of allogeneic MPC directly after the AMI resulted in preserved global and regional cardiac function, evoked by reduced infarct size, increased perfusion and reduced adverse remodeling.
- Stem cell therapy
- Myocardial infarction, STEMI
- Interventional cardiology
- Regenerative medicine stem cells
- © 2011 by American Heart Association, Inc.