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 x 10(6) 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.