Comparison of Magnetic Intensities for Mesenchymal Stem Cell Targeting Therapy on Ischemic Myocardial Repair: High Magnetic Intensity Improves Cell Retention but Has no Additional Functional Benefit

摘要

Magnetic targeting has the potential to enhance the therapeutic effects of stem cells through increasing retention of transplanted cells. To investigate the effects of magnetic targeting intensities on cell transplantation, we performed different magnetic intensities for mesenchymal stem cell (MSC)-targeting therapy in a rat model of ischemia/reperfusion. Rat MSCs labeled with superparamagnetic oxide nanoparticles (SPIOs) were injected into the left ventricular (LV) cavity of rats during a brief aorta and pulmonary artery occlusion. The 0.15 Tesla (T), 0.3 T, and 0.6 T magnets were placed 0 similar to 1 mm above the injured myocardium during and after the injection of 1 x 10(6) MSCs. Fluorescence imaging and quantitative PCR revealed that magnetic targeting enhanced cell retention in the heart at 24 h in a magnetic field strength-dependent manner. Compared with the 0 T group, three magnetic targeting groups enhanced varying cell engraftment at 3 weeks, at which time LV remodeling was maximally attenuated, and the therapeutic benefit (LV ejection fraction) was also highest in the 0.3 T groups. Interestingly, due to the low MSC engraftment resulting from microvascular embolisms, the 0.6 T group failed to translate into additional therapeutic outcomes, though it had the highest cell retention. Magnetic targeting enhances cell retention in a magnetic field strength-dependent manner. However, too high of a magnetic intensity may result in microembolization and consequently undermine the functional benefits of cell transplantation.