Stem Cell Labeling with Superparamagnetic Iron Oxide Nanoparticles Using Focused Ultrasound and Magnetic Resonance Imaging Tracking

Magnetosonoporation (MSP) is a relatively safe and efficient approach for instant MR stem cell labeling. In this study, the physical and magnetic properties of different formulations of synthesized superparamagnetic iron oxide nanoparticles (SPION) were characterized. Then, a closed MSP apparatus using focused ultrasound was designed and the feasibility of MSP stem cell labeling using focused ultrasound was validated by evaluating the proliferation, migration and differentiation of the magnetically labeled cells. Subsequently, MSP/SPION labeled neural stem cells (NSCs) were transplanted into the contralateral striatum of glioma-bearing nude mice, and their migration was monitored using magnetic resonance imaging (MRI) in vivo. The results indicated that SPION-1 with the largest size (28.43 +/- 9.55 nm) had the highest T-2 relaxivity (136.62 Fe mM(-1) S-1) and the best MRI contrast effect. Without additional transfection reagents, NSCs were labeled with SPION using focused ultrasound in vitro and the safety of MSP stem cell labeling was validated with the optimized MSP technique. Finally, confirmed by histological evaluation, pronounced signal attenuation on T-2-weighted images demonstrated the intracranial tumor tropism of NSCs could be monitored non-invasively by MRI. In conclusion, MSP cell labeling using focused ultrasound is a promising technique and the closed device is feasible, convenient and safe for instant magnetic stem cell labeling and MRI cell tracking.