Abstract 17744: Allogeneic Intracoronary Mesenchymal Stem Cells (icMSCs) and Cardiosphere-Derived Cells (icCDCs) Stimulate Comparable Endogenous Myocyte Regeneration Throughout the Left Ventricle in Swine With Hibernating Myocardium
Background: Autologous icMSCs and icCDCs improve function of ischemic myocardium but the role of reverse remodeling in normally perfused remote regions and the source of new myocytes is unclear. We tested the hypothesis that allogeneic cells promote myocyte regeneration throughout the left ventricle (LV) using a study design that allowed blinded comparison of icCDCs vs. icMSCs and the assessment of cell fate.
Methods: Immunosuppressed swine (cyclosporine 200 mg/day; N=26) with a chronic LAD stenosis were randomized to receive vehicle, ~35 x 106 allogeneic icMSCs, or ~35 x 106 allogeneic icCDCs. Cells were infused into the 3 major coronary arteries at 106 cells/min under continuous flow. Myocardial function and morphometric indices of myocyte and LV remodeling were assessed 1 month later. Y-FISH was performed to assess donor cell fate in sex-mismatched recipients (n=3 each cell type).
Results: Ischemic LAD and non-ischemic remote zone wall thickening increased after cell therapy vs. vehicle controls (Table). This functional improvement was associated with substantial myocyte regeneration throughout the LV reflected by increases in myocyte nuclear density and reciprocal reductions in myocyte diameter. All changes were similar between icMSC- and icCDC-treated animals. Intracoronary cell therapy yielded ~40,000 to 60,000 new myocytes/cm2 with few cells arising from the donor (icMSCs: 6 ± 2 Y+ cells/cm2; icCDCs: 8 ± 3 Y+ cells/cm2). Myocyte regeneration after cell treatment did not result in organ hypertrophy, as LV mass was similar among all groups.
Conclusion: These results demonstrate comparable efficacy of allogeneic icMSCs and icCDCs to treat ischemic LV dysfunction by stimulating endogenous myocyte regeneration throughout the heart. Functional improvement and new myocyte generation occur in both ischemic and remote myocardium with only ~1 in 10,000 new cells arising from allogeneic donor cells, supporting paracrine signaling as the primary mechanism.
- Ischemic heart disease
- Regenerative medicine stem cells
- Stem cell therapy
- Stem/progenitor cells
- Ventricular remodeling
- © 2013 by American Heart Association, Inc.