Gadolinium hexanedione nanoparticles for stem cell labeling and tracking via magnetic resonance imaging

The ability to trace transplanted stem cells and monitor their tissue biodistribution is prerequisite to an understanding of cellular migration after transplantation. Therefore, a new magnetic resonance imaging (MRI) contrast agent made of gadolinium hexanedione nanoparticles (GdH-NPs) was developed as a cell tracking agent. The GdH-NPs were fabricated by the microemulsion process. The physical characteristics, biocompatibility, and T1-MRI signal enhancement of these NPs were analyzed and evaluated for stem cell tracking. In this study, the size of the synthesized GdH-NPs was about 140 nm, and it had greater image enhancement ability than commercial gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). From the biocompability test, we found GdH-NPs were nontoxic for human mesenchymal stem cells (hMSCs). The expression of surface antigens of hMSCs after culture with GdH-NPs was examined, and it showed no difference from the control group. The results of transmission electron microscopy (TEM) imaging for labeled hMSCs showed GdH-NPs were accumulated in the cells by the endocytotic pathway. The accumulation of GdH-NPs in hMSCs was three times higher in comparison to Gd-DTPA. Human MSCs labeled with low concentration of GdH-NPs (10 μg/mL) hold better signals in cellular MR image. We conclude GdH-NPs can be used to label hMSCs in vitro with greater T1 image-enhancing property and without affecting cell quality. Finally, GdH-NPs have great potential as a contrast agent for stem cell tracking by MRI methodology.