Grafted Neural Stem Cells Show Lesion-Specific Migration in Radiation-Injured Rat Brains

Neural stem cells (NSCs) exhibit preferential homing toward some types of brain lesion, but their migratory property during radiation brain injury (RBI) remains unexplored. Here, we use the superparamagnetic iron oxide (SPIO)-labeled magnetic resonance imaging (MRI) technology to determine the migration of transplanted NSCs in two partial RBI models in real time, created by administering 30-55 Gy of radiation to the right or posterior half of the adult rat brain. SPIO-labeled NSCs were stereotactically grafted into the uninjured side one week after RBI. The migration of SPIO-labeled NSCs in live radiation-injured brains was traced by MRI for up to 28 days after engraftment and quantified for their moving distances and speeds. A high labeling efficiency (>90%) was achieved by incubating NSCs with 100μg/ml of SPIO for 12-24 hours. Upon stereotactic transplantation into the healthy side of the brain, SPIO-labeled NSCs were distinctively detected as hypointense signals on T2-weighted images (T2WI), showed sustained survival for up to 4 weeks, and exhibited directional migration to the radiation-injured side of the brain with a speed of 86-127 μm/day. The moving kinetics of grafted NSCs displayed no difference in brains receiving a high (55 Gy) vs. moderate (45 Gy) dose of radiation, but was slower in the right RBI model than in the posterior RBI model. This study shows that NSCs can be effectively labeled by SPIO and traced in vivo by MRI, and that grafted NSCs exhibit directional migration toward RBI sites in a route-dependent but radiation dose-independent manner.