Abstract
IntroductionRetrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. Poor cell retention is the major obstacle to the establishment of this method as the preferred route for cell delivery. Here, we explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction.MethodsRat mesenchymal stem cells were labeled with superparamagnetic oxide nanoparticles. The magnetic responsiveness of MSCs was observed while cells flowed through a tube that served as a model of blood vessels in a 0.6-Tesla magnetic field. In a Sprague–Dawley rat model of acute myocardial infarction, 1 × 106 magnetic mesenchymal stem cells were transjugularly injected into the left cardiac vein while a 0.6-Tesla magnet was placed above the heart. The cardiac retention of transplanted cells was assessed by using quantitative Y chromosome-specific polymerase chain reaction, cardiac magnetic resonance imaging, and optical imaging. Cardiac function was measured by using echocardiography, and histologic analyses of infarct morphology and angiogenesis were obtained.ResultsThe flowing iron oxide-labeled mesenchymal stem cells were effectively attracted to the area where the magnet was positioned. Twenty-four hours after cellular retrocoronary delivery, magnetic targeting significantly increased the cardiac retention of transplanted cells by 2.73- to 2.87-fold. Histologic analyses showed that more transplanted cells were distributed in the anterior wall of the left ventricle. The enhanced cell engraftment persisted for at least 3 weeks, at which time, left ventricular remodeling was attenuated, and cardiac function benefit was improved.ConclusionsThese results suggest that magnetic targeting offers new perspectives for retrograde coronary venous delivery to enhance cell retention and subsequent functional benefit in heart diseases.
Highlights
Retrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty
Cell therapy is a promising approach for acute myocardial infarction (AMI) and heart failure, and its efficacy largely depends on cell homing, retention, and engraftment within the injured myocardium
Few data exist on the efficacy of magnetic targeting on retrograde cell retention
Summary
Retrograde coronary venous infusion is a promising delivery method for cellular cardiomyoplasty. We explored whether magnetic targeting could enhance retrograde cell retention in a rat model of myocardial infarction. Cell therapy is a promising approach for acute myocardial infarction (AMI) and heart failure, and its efficacy largely depends on cell homing, retention, and engraftment within the injured myocardium. Magnetic targeting strategies have been successfully introduced to attract cells infused via intramyocardial [15] and intracoronary [16,17] routes to the ischemic heart. This technique has been proven to enhance cell retention, engraftment, and functional benefits. Few data exist on the efficacy of magnetic targeting on retrograde cell retention
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