Regenerative capacity of intravenous autologous, allogeneic and human mesenchymal stem cells in the infarcted pig myocardium – complicated by myocardial tumor formation

Abstract

Objectives. Intravenous delivery of mesenchymal stem cells (MSCs) is an attractive approach for regeneration of infarcted myocardium. However, its efficacy is not well-defined in large animals. Methods. Pigs (n =8) received intravenously autologous, allogeneic porcine or human MSCs (1×106 per kg bodyweight) labeled with fluorescent dye 48 hours post proximal LAD occlusion. Infarct size, histology and myocardial function were assessed 4 weeks later. Results. Labeled MSCs migrated in the peri-infarct region resulting in improved myocardial function. Infarct size was larger in the control group (32±7%) compared to autologous (19±7%, p =0.008), allogeneic (24±4%, p =0.01) and human MSCs (26±5%, p =0.03). Fractional area shortening significantly increased after 4 weeks in pigs receiving autologous MSCs (34±7%, p =0.001), allogeneic MSCs (28±2%, p =0.004) and human MSCs (24±5%, p =0.027), but was lower in the control group (23±3%, n.s.). However, substantial callus formation and a non-malignant cardiac “tumor” containing mesenchymal tissue was observed in one animal treated with human MSCs. Conclusions. Intravenously administered MSCs prevent pathologic remodeling and scar formation but bare potential risks from inflammatory-related products.