title: Ultrasound-mediated microbubble destruction enhances the therapeutic effect of intracoronary transplantation of bone marrow stem cells on myocardial infarction.
abstract: OBJECTIVE
  The combination of intracoronary transplantation and ultrasound-mediated microbubble destruction may promote effective and accurate delivery of bone marrow stem cells (BMSCs) into the infarct zone. To test this hypothesis in this study we examined the effectiveness of ultrasound-mediated microbubble destruction in combination with intracoronary transplantation of BMSCs for the treatment of myocardial infarction in canine model of acute myocardial infarction.
  
  
  METHODS
  The dogs were randomly assigned to four groups: PBS, ultrasound-mediated microbubble destruction, BMSCs, BMSCs together with ultrasound-mediated microbubble destruction. At 28 days post-surgery, cardiac function and the percentage of perfusion defect area to total left ventricular perfusion area (DA%) were determined by myocardial contrast echocardiography. Nitro blue tetrazolium staining was performed to determine myocardial infarct size, hematoxylin and eosin staining for assessing microvascular injury, Masson's staining for analyzing myocardial tissue collagen, immunohistochemical analysis of α-actin to measure cardiac contractile function and of BrdU-labeled myocardial cells to measure the number of the BMSCs homing to the infarcted region.
  
  
  RESULTS
  The transplantation of BMSCs significantly improved heart function and DA% (P < 0.05). The group that received ultrasound-mediated microbubble destruction with BMSCs transplantation showed the most improvement in heart function and DA% (P < 0.05). This group also showed a denser deposition of BMSCs in the coronary artery and more BrdU positive cells in the infarcted region, had the maximum number of α-actin positive cells, showed the smallest myocardial infarct area compared to other groups (P< 0.05).
  
  
  CONCLUSIONS
  Ultrasound-mediated microbubble destruction increases the homing of BMSCs in the target area following intracoronary transplantation, which allows more BMSCs to differentiate into functional cardiomyocytes, thereby reducing myocardial infarct size and improving cardiac function.
authors.affiliation: Department of Emergency Surgery, First Hospital of Jilin University Changchun 130021, Jilin, China.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Radiation Medicine, School of Public Health of Jilin University Changchun 130021, Jilin, China.
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Affiliated Hospital of Beihua University Jilin 132011, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Emergency Surgery, First Hospital of Jilin University Changchun 130021, Jilin, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D004285:Dogs; D004452:Echocardiography; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells; D045423:Microbubbles; D009203:Myocardial Infarction / Q000628:therapy*; D018084:Ultrasonography, Interventional
keywords: Myocardial infarction; bone marrow stem cells; diagnostic ultrasound-mediated microbubble destruction; intracoronary transplantation