Cell motility of neural stem cells is reduced after SPIO-labeling, which is mitigated after exocytosis.

MRI is used for tracking of superparamagnetic iron oxide (SPIO)-labeled neural stem cells. Studies have shown that long-term MR tracking of rapidly dividing cells underestimates their migration distance. Time-lapse microscopy of random cellular motility and cell division was performed to evaluate the effects of SPIO-labeling on neural stem cell migration. Labeled cells divided symmetrically and exhibited no changes in cell viability, proliferation, or apoptosis. However, SPIO-labeling resulted in decreased motility of neural stem cells as compared with unlabeled controls. When SPIO-labeled neural stem cells and human induced pluripotent stem cells were transplanted into mouse brain, rapid exocytosis of SPIO by live cells was observed as early as 48 h postengraftment, with SPIO-depleted cells showing the farthest migration distance. As label dilution is negligible at this early time point, we conclude that MRI underestimation of cell migration can also occur as a result of reduced cell motility, which appears to be mitigated following SPIO exocytosis.