Ultrasound-mediated microbubble destruction enhances the efficacy of bone marrow mesenchymal stem cell transplantation and cardiac function.

1. Application of ultrasound (US) to intravascular microbubble (MB) contrast agents causes small capillary ruptures. The purpose of the present study was to examine the effects of US-mediated MB destruction on bone marrow mesenchymal stem cell (BMSC) transplantation into the infarcted myocardium and to evaluate whether this approach could improve cardiac function. 2. Ultrasound was applied to the anterior chest of rabbits after intravenous injection of MB followed by infusion of BMSC. There were four groups investigated: (i) a control group, in which neither US nor MB were used prior to infusion of BMSC; (ii) one group subjected to US alone prior to infusion of BMSC; (iii) another group injected with MB prior to infusion of BMSC; and (iv) a group in which US was applied to MB prior to the infusion of BMSC. Cardiac function was evaluated by echocardiography 24 h and 4 weeks after cell transplantation. All rabbits were killed to enable histological and immunochemical examination. 3. Echocardiography 24 h after infusion of BMSC indicated no difference in cardiac function between any of the groups, as assessed by left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimensions (LVDD), left ventricular systolic diameter (LVSD) and fractional shortening (FS%; all P > 0.05). However, 4 weeks after BMSC transplantation, there was a significant improvement in LVEF in the group subjected to US plus MB compared with the control, US alone and MB alone groups (59.5 +/- 3.5, 52.5 +/- 5.5, 52.8 +/- 5.2 and 51.1 +/- 3.5%, respectively; all P < 0.05). In addition, treatment with US plus MB significantly reduced LVDD and LVSD and increased capillary density in the infarcted area. 4. In conslusion, the results of the present study indicate that using US-mediated MB destruction prior to BMSC transplantation into the infarcted myocardium improves the effectiveness of cardiac cell therapy and cardiac function in rabbits.