Abstract 3693: Hybrid Therapy With Pravastatin and Nonautologous Intracoronary Mesenchymal Stem Cells (MSCs) Synergistically Facilitates Cardiac Repair in Swine With Ischemic Cardiomyopathy
Background: We have previously demonstrated that pravastatin and autologous MSCs each increase circulating bone marrow progenitor cells and stimulate myocyte regeneration in swine with hibernating myocardium. Since patients are usually receiving statins, we performed the present study to determine whether MSCs improve function when administered on a pravastatin background in the presence of global systolic LV dysfunction.
Methods: Swine with chronic LAD and LCX stenoses to produce ischemic cardiomyopathy received pravastatin (80mg/day) alone (n=4) or with 20×106 i.c. nonautologous MSCs (n=8) and results were compared to untreated animals (n=6). We assessed coronary perfusion (microspheres) and function at baseline and 4-weeks after treatment. We quantified myocytes in the cell cycle with Ki-67, mitosis with phospho-Histone H3 (pHH3) along with myocyte nuclear density to assess proliferation.
Results: DAPI labeled MSCs were predominantly localized in interstitial space of myocytes. When MSCs were administered with pravastatin, systolic LAD ΔWT increased from 2.5±0.3 mm to 5.0±0.6 mm (p<0.01) with no change in coronary flow. Immunohistochemistry (Table⇓) demonstrated that combined therapy increased both Ki-67+ and pHH3+ myocytes significantly more than untreated animals or those receiving only pravastatin. These produced significant increases in myocyte nuclear density. This reflected small immature myocytes which led to a reduction in mean myocyte diameter.
Conclusion: These data indicate that hybrid therapy with pravastatin and nonautologous MSCs in a model of ischemic cardiomyopathy
Amplifies the number of Ki67 and pHH3 positive myocytes in the heart and
Increases myocyte nuclear density with reduced myocyte size.
The data support the notion that pravastatin and nonautologous MSCs synergistically enhance endogenous cardiac repair in ischemic cardiomyopathy.