Transplantation of stem cells may improve regional perfusion and post-
infarct ventricular function, but the optimal dose and efficacy of cell delivery via the intravenous route has not been determined. This study tested the hypothesis that
intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) enhances regional perfusion and improves ventricular function after
myocardial infarction. In a closed-chest pig model, the LAD coronary artery was occluded for 75 min by angioplasty balloon inflation followed by 12 weeks of reperfusion. After 15 min of reperfusion, pigs randomly received 1 of 4 treatments: (1) Vehicle (Control, n = 10); (2) 1 x 10(6) MSCs/kg (1 mill, n = 7); (3) 3 x 10(6) MSCs/kg (3 mill, n = 8) and (4) 10 x 10(6) MSCs/kg (10 mill, n = 8). Angiogenesis was demonstrated by immunohistochemical staining, myocardial blood flow (steady state and
vasodilator reserve) was measured using 15 microm neutron-activated
microspheres, and cardiac function was determined by contrast left ventriculography (ejection fraction) and pressure-volume relationships. After 12 week of reperfusion,
von Willebrand Factor-positive vessels and tissue
vascular endothelial growth factor (
VEGF) expression in the
scar zone was significantly greater in all MSCs-treated animals relative to Control. Steady state myocardial blood flow in the
scar tissue was comparable among groups. However,
adenosine recruited
vasodilator reserve in the
scar zone induced by intracoronary
adenosine was significantly higher in the MSC-treated animals compared to Control. Furthermore, preload-recruitable
stroke work and systolic performance were significantly greater compared to Control. In conclusion, these data demonstrate that intravenous delivery of MSCs during early reperfusion augments vasculogenesis, enhances regional perfusion, and improves post-
infarct ventricular function. The results suggest that
intravenous infusion of MSCs is an effective modality for the treatment of
ischemia/reperfusion induced myocardial injury.