Abstract 19681: The Combination of Allogeneic Mesenchymal Stem Cells and Cardiac Stem Cells Produce Synergistic Effects in Cardiac Regeneration
Introduction: Combining mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) has synergistic effects in reducing scar size and improving cardiac function for the treatment of ischemic cardiomyopathy. MSCs are favorable allogeneic candidates as they can evade immunologic response. We hypothesized that the allogeneic application of combined MSCs and CSCs promote cardiac regeneration without provoking immunologic reactions.
Methods: We tested the hypothesis in a placebo-controlled blinded swine infarct model by combining allogeneic MSCs and CSCs, and comparing with either cell type alone [MSC + CSC (n = 7), MSC (n = 8), CSC (n = 4), placebo (n = 6)]. Twelve weeks after female Gottingen swine underwent ischemic reperfusion injury, they were randomized to receive transendocardial injection of allogeneic cells derived from male Yorkshire swine (MSC; 2 х 108 cells, CSC; 1 х 106 cells, MSC + CSC, placebo; Plasmalyte A). Swine were assessed by cardiac magnetic resonance imaging and pressure volume loops. We further tested for immune response utilizing mixed lymphocyte reaction (MLR), histological analyses of the heart, and whole body necropsy.
Results: Scar size (p = 0.83) and cardiac enzyme deviation (troponin I, p = 0.33) prior to treatment were similar between groups. The combination of MSCs and CSCs reduced scar size by 11.9 ± 5.0% (p = 0.0014), and suppressed negative remodeling by offsetting the increase of end systolic volume 6.3 ± 1.3 ml when compared to placebo (p = 0.01). Cardiac function improved as assessed by end-systolic pressure volume relation by 0.97 ± 0.19 (p = 0.048). All improved parameters were superior in the combination treated group when compared to either cell type. MSC + CSC and MSC alone treated groups elicited a decrease in MLR (p = 0.0005). Histological analysis revealed nodular inflammatory infiltrates confined to the injection sites in 20 to 25% of MSC and combination treated swine (p = NS) without evidence of myocardial damage. There were no incidences of clinical hyperacute and acute immune rejection up to 3 months post treatment.
Conclusion: The combination of allogeneic MSCs and CSCs in a swine model of chronic ischemic cardiomyopathy demonstrates synergistic effects for cardiac regeneration without adverse immunological reaction.
Author Disclosures: M. Natsumeda: None. V. Florea: None. A.M. Castellanos: None. B.A. Tompkins: None. A.M. Landin: None. J. Fritsch: None. K. Collon: None. L. Vincent: None. A.J. Kanelidis: None. J. Rodriguez: None. M. Rosado: None. I.H. Schulman: None. W. Balkan: None. R. Mitrani: None. J. Hare: Ownership Interest; Significant; Vestion Inc.. Consultant/Advisory Board; Modest; Vestion Inc..
- © 2016 by American Heart Association, Inc.