7.0 tesla high resolution MRI study on intracerebral migration of magnet-labeled neural stem cells in a mouse model of Alzheimer's disease

Abstract Objective To observe the migration characteristics of neural stem cells (NSCs) labeled with the MRI contrast agent superparamagnetic iron oxide (SPIO) in the brain of APP/PS1 transgenic mice with Alzheimer's disease (AD) by 7.0 T high resolution MRI. Methods C57BL/6 mouse NSCs were cultured, amplified, labeled with Feridex and Poly- l -lysine (FE-PLL) and evaluated by transmission electron microscopy (TEM). Using the random number table method, 24 APP/PS1 transgenic AD mice aged 12 months were equally assigned to two groups: animals in group A were transplanted with FE-PLL labeled NSCs and those in group B were transplanted with non-labeled NSCs in the right hippocampus. Twelve wild-type mice of the same age and born from the same litter were used as the control group (group C) and transplanted with FE-PLL labeled NSCs. Using the 7.0 T high resolution MR scanner, the transplanted NSCs were traced in vivo at 1 day, 1 and 2 weeks after cell transplantation. The MRI findings were compared with the histopathological findings. Results C57BL/6 mouse NSCs were cultured and amplified successfully. TEM showed large amounts of iron-containing particles in the cytoplasm of transplanted cells. MRI in group A showed the presence of spheroid low signals at the injection point of the hippocampus on T 2 *WI one day after transplantation; one weeks later, the low signals were seen diffusing to the surroundings along the injection point, and covering almost the whole hippocampal area but the intensity of the low signals became weaker gradually; two weeks after transplantation, almost all low signals disappeared. In group B, no significant change in low signals was observed in the transplantation area at all designated time points. Although low signals were also observed in the hippocampus after transplantation of FE-PLL labeled NSCs in group C, their size and location remained almost unchanged. Prussian blue staining showed that migration of the FE-PLL labeled NSCs in the hippocampus of the AD mice was consistent with the MRI findings at all designated time points. Conclusion NSCs underwent diffuse and non-directional migration to the surroundings after they were transplanted to the hippocampus of APP/PS1 transgenic AD mice, and this migration pattern could be traced in vivo by MRI when they were labeled with magnet.