Ultrasound-mediated microbubble promotes bone marrow mesenchymal stem cell transplantation for myocardial infarction⋆♦

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Abstract

BACKGROUND:

Ultrasound-mediated microbubble has been widely used in clinical myocardial microcirculation diagnosis, and its safety has been verified. Ultrasound target microvesicle can destroy skeletal nuscle blood capillary and local erythrocytes, and promote cells crossing endothelial physiologic barrier.

OBJECTIVE:

To study whether ultrasound-mediated microbubble enhances bone marrow mesenchymal stem cell (BMSC) transplantation for myocardial infarction.

DESIGN, TIME AND SETTING:

The randomized controlled animal study was performed at the Medical College, Southeast University from October 2006 to May 2008.

MATERIALS:

A total of 20 pigs aged 2 months, and randomly assigned into ultrasound microvesicle group (n=12) and cell control group (n=8). Opaque medium SonoVue (J20030117) was purchased from Bolaixinyi, Shanghai.

METHODS:

Bone marrow was sterilely isolated. BMSCs were isolated and purified by the density gradient centrifugation. In both groups, acute myocardial infarction models were established. After 14 days, 2.4 mL SonoVue was infused into the left anterior descending branch of pigs in the ultrasound microvesicle group via the OTW Foley's tube through the coronary artery. Myocardial infarct region received 1 MHz, 2 W/cm2 ultrasonic radiation for 90 seconds. Subsequently, superparamagnetic iron oxide-labeled BMSCs (5×106) were injected into pigs. In the cell control group, pigs only were subjected to BMSCs.

MAIN OUTCOME MEASURES:

Heart function of pigs was checked by 64-spiral CT. Myocardial tissue was observed under an optical microscope. Ultrastructure of vascular endothelial cells was observed under the electron microscope.

RESULTS:

Compared with that 1 day pretransplantation, ejection fraction of the left ventricle significantly increased at 6 weeks following transplantation, and the increase was higher in the ultrasound microvesicle group than in the cell control group (P < 0.01). Compared with the cell control group, number of Prussian blue-positive cells was more in the ultrasound microvesicle group (P < 0.01), and mainly distributed in myocardial infarct region. In 2 cases, Prussian blue-positive cells differentiated into new vascular endothelial cells. The density of heart muscle capillary was higher in the infarct region (P < 0.05). In both groups, myocardial ultrastructure had no difference, but the gap of blood vessel endothelium widened in the ultrasound microvesicle group immediately after transplantation.

CONCLUSION:

Ultrasound-mediated microbubble can enhance auto-BMSCs myocardial transplantation, promote myocardial, and finally improve cardiac function.

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