Cell Combination Therapy (MSC + CSC) Reduces Scar Size and Promotes Mitosis of Endogenous Cells in a Swine Chronic Myocardial Infarction Model
Delayed enhancement cardiac magnetic resonance short-axis representative images showing and quantifying the chronologic change of scar size in placebo and combination cell treatment groups pre- and post-transendocardial stem cell injection (TESI), from both allogeneic (A) and autologous (C) studies in swine MI. Graphs show that change in scar mass, as a percentage of left ventricular (LV) mass, decreased significantly following TESI of allogenic and autologous cell combination and mesenchymal stem cell therapies compared to placebo or cardiac stem cell therapy alone. *p < 0.05 within group, **p < 0.001 MSC + CSC versus placebo at all time points post-TESI, ***p < 0.0001 MSC + CSC or MSC versus placebo at all time points post-TESI, Ϯp < 0.05 MSC versus placebo at all time points post-TESI. MSC, mesenchymal stem cell; CSC, ckit+ cardiac stem cell. (B and D) Representative confocal microscopy images showing mitosis of cardiomyocytes in response to allogeneic (B) or autologous (D) combination stem cell treatment, using the mitosis-specific marker phospho-histone H3 (PHH3). Graphs represent PHH3 cardiomyocytes/slide in the remote (allogeneic) and border (autologous) zones. *p < 0.05 MSC + CSC versus placebo. Adapted from Natsumeda et al.41 (allogeneic cell study) and Karantalis et al.48 (autologous cell study).