Myocardium-targeted transplantation of mesenchymal stem cells by diagnostic ultrasound-mediated microbubble destruction improves cardiac function in myocardial infarction of New Zealand rabbits

BackgroundTherapeutic ultrasound-mediated microbubble destruction has been applied in the targeted delivery of genes, drugs and stem cells. We intended to study whether diagnostic US irradiating lipid-coated microbubble destruction combined with bone-marrow derived MSC infusion could enable the targeted delivery of MSCs into the myocardium and improve cardiac function of the myocardial infarction of New Zealand rabbits.MethodsDiagnostic ultrasound was applied to the anterior chest for 10 min after intravenous injection of lipid-coated microbubble followed by infusion of BM-MSCs. Echocardiography, histological examination, and western blotting were performed 4 weeks after cell transplantation.ResultsThe cardiac function (assessed by fractional shortening and ejection fraction) was markedly improved by US + Microbubble + MSC treatment. The number of capillaries stained by HE in US + Microbubble + MSC group (47 ± 23) was much greater than that of the MSCs infusion group (26 ± 7), US + Microbubble group(22 ± 5) and PBS infusion group (19 ± 10), P < 0.01. US + Microbubble stimulation induced the expression of adhesion molecule (VCAM-1) in capillaries and enhanced the myocardial permeability of microvessels. US + Microbubble-mediated supply of MSCs increased the level of VEGF in ischemic myocardium. Area of cardiac fibrosis in the US + Microbubble + MSC group was significantly decreased by 25.6%,40.1% and 46.8% when compared with MSC infusion group, US + Microbubble group and PBS infusion group, respectively.ConclusionsThis non-invasive cell delivery system may be useful as a novel and efficient approach for angiogenic cell therapy to the infarcted myocardium.