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


METHODS
Diagnostic 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.


RESULTS
The 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.


CONCLUSIONS
This non-invasive cell delivery system may be useful as a novel and efficient approach for angiogenic cell therapy to the infarcted myocardium.
Xu
Ya-Li
YL
Department of Ultrasound, Second affiliated Hospital, Third Military Medical University, Chongqing 400037, PR China. xuyali1976@163.com
Gao
Yun-Hua
YH
Liu
Zheng
Z
Tan
Kai-Bin
KB
Hua
Xing
X
Fang
Zhen-Qiang
ZQ
Wang
Ya-Li
YL
Wang
Ya-Jie
YJ
Xia
Hong-Mei
HM
Zhuo
Zhong-Xiong
ZX
D000818:Animals; D015153:Blotting, Western; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003326:Coronary Circulation; D005355:Fibrosis; D005434:Flow Cytometry; D045164:Mesenchymal Stem Cell Transplantation / Q000295:instrumentation* / Q000379:methods*; D045423:Microbubbles; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D011817:Rabbits; D014184:Transplantation, Homologous; D014465:Ultrasonics; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D016277:Ventricular Function, Left
D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A