Dose-Dependent Effects of Intravenous Allogeneic Mesenchymal Stem Cells in the Infarcted Porcine Heart

Intravenous delivery of mesenchymal stem cells (MSCs) preserves myocardial function after infarction. This dose-escalating study was performed to examine pathologic remodeling and scar formation in a pig model of permanent coronary occlusion without restoration of reperfusion. MSCs labeled with fluorescent dye 48 h or saline (negative control, n = 8) were given intravenously 48 h post proximal left anterior descending artery occlusion. Animals received either autologous or allogeneic MSCs in doses from 1 × 103 up to 1 × 106 per kg bodyweight from an unrelated donor pig. Infarct size and myocardial function were assessed after 1 month. Morphologic analysis revealed that labeled autologous MSCs migrated in the peri-infarct region resulting in smaller infarct size (19 ± 7% vs. 32 ± 7%, p < 0.008) and higher fractional area shortening (33 ± 7% vs. 21 ± 3%, p < 0.001). Similarly, allogeneic MSCs had dose-dependent beneficial effects on cardiac function, statistically significant at 1 × 105 and 1 × 106 cells pe...