Abstract 11090: Intracoronary Infusion of Allogeneic Cardiosphere-Derived Cells (icCDCs) Stimulates Endogenous Myocyte Proliferation and Inhibits Apoptosis in Swine with Ischemic Cardiomyopathy
Background: Previous studies have demonstrated the efficacy of autologous icCDCs in swine with healed infarction as well as chronic hibernating myocardium. We tested the hypothesis that unmatched allogeneic icCDCs could facilitate cardiac repair in ischemic cardiomyopathy where ongoing cell death from apoptosis leads to myocyte loss and hypertrophy.
Methods: Swine (n=14) with ischemic cardiomyopathy from chronic stenoses on both LAD and LCX were studied 4 weeks after instrumentation. Untreated animals (n=6) were compared to those receiving 20 x 106 allogeneic icCDCs (n=8) infused into the 3 major coronary distributions after cyclosporine (200mg/day) immunosuppression. We assessed function (echo) at baseline and 4-weeks after treatment. Myocyte proliferation (Ki67), mitosis (phospho Histone H3; pHH3) and apoptosis (TUNEL) were assessed with immunohistochemistry. Myocyte regeneration was quantified by assessing myocyte nuclear density and myocyte size.
Results: Sex mismatched allogeneic icCDCs demonstrated that 3.2 ± 1.6% of the injected cell number were retained in the heart at 4 weeks with myocyte differentiation very rare. After icCDCs, both LAD wall thickening and ejection fraction improved (p<0.05, Table). Administration of icCDCs stimulated endogenous myocyte proliferation (Ki67, pHH3) while decreasing myocyte apoptosis 7-fold. As a result of these beneficial effects, myocyte number (nuclear density) increased two-fold with a reduction in myocyte cell diameter.
Conclusion: These data indicate that allogeneic icCDCs rarely differentiate into cardiomyocytes yet produce prominent endogenous myocyte proliferation and prevent myocyte cell death. These effects all contribute to an improvement in regional and global LV function in viable dysfunctional myocardium. Thus, allogeneic icCDC infusion may afford an easily implemented approach to reverse LV dysfunction in patients with decompensated heart failure and ongoing myocyte cell death.
- © 2012 by American Heart Association, Inc.