Effects of ultrasound-exposed microbubbles pretreatment on bone marrow mesenchymal stem cells homing to ischemic myocardium

Abstract

Objective To explore the effects of pretreatment of bone marrow mesenchymal stem cells (BMSCs) by ultrasound-exposed microbubbles (UM) on both homing to ischemic myocardium and cardiac function after acute myocardial infarction (AMI). Methods Rats of AMI model established by ligation of left anterior descending coronary artery were divided into four groups randomized: phospho-buffered saline (PBS) group, stem cells treatment (SCT) group, ultrasound and stem cells treatment (USCT) group, and UM stem cells treatment (UMSCT) group, and each group was injected with PBS, stem cells, US-pretreated stem cells and UM-pretreated stem cells through the caudal veins after AMI respectively. Homing of BMSCs to the ischemic myocardium was examined by confocal microscopy at 48 h after implantation, and cardiac function was examined by ultrasonic cardiogram (UCG) after 4 weeks. Masson staining was used to examine the changes of local ischemic cardiac tissues, and immunohistochemistry was used to detect the density of local neo-capillaries (CD31). Results 1) The numbers of CM-Dil-positive cells counted under confocal microscopy in the ischemic myocardial tissues of each groups 48 hours after implantation were not the same: there was no significant difference of the numbers of positive cells between USCT group (19.67±2.08) and SCT group (18.67±2.08). However, the number of positive cells in the UMSCT group (39.33±3.06) was larger than that in USCT group and SCT group (P 0.05], but both were better than that in PBS group [LVEF (20.52±1.88)%, LVFS (9.55±0.85)%, P 0.05], while both were significantly smaller than that in PBS group [(45.2±1.4)%, P<0.05]. The percentages of AMI areas in the UMSCT group [(25.8±1.0)%] were significantly smaller than that in USCT group and SCT group (P<0.05). The density of neo-capillaries (25.9±1.3) in USCT groups had no difference compared with that in SCT group (25.2±1.3), while both were significantly higher than that in PBS group (17.6±1.1, P<0.05); the density of neo-capillaries (33.2±1.6) was significantly higher in UMSCT group than that in both USCT group and SCT group (P<0.05), which were examined by immunohistochemistry. Conclusions Homing to ischemic myocardium of BMSCs transplanted intravenously could be promoted by UM pretreatment, which stimulates development of capillaries, reduces AMI areas, and improves the cardiac function after AMI. Key words: Sonication; Microbubbles; Mesenchymal stem cells; Myocardial infarction; Ventricular functio, left