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Magnetic Resonance Imaging Tracking of Induced Pluripotent Stem Cells-Induced Neural Stem Cells in Traumatic Brain Injury Rats


 
 
 Induced pluripotent stem cells (iPS cells) are promising cell source for stem cell replacement strategy applied to brain injury caused by traumatic brain injury (TBI) or stroke. Neural stem cell (NSCs), derived from iPS cells could aid the reconstruction of brain tissue and the restoration of brain function. However, how to trace the fate of iPS cells in host brain is still a challenge.
 
 
 
 In our study, iPS cells were derived from skin fibroblasts using the 4 classic factors Oct4, Sox2, Myc, and Klf4. Then these iPS cells were induced to differentiate into NSCs, which were incubated with superparamagnetic iron oxides (SPIOs) in Vitro. Next, 30 TBI rat models were prepared and divided into 3 groups (n = 10). One week after brain injury, group A and B rats received NSCs (labeled with SPIOs) implantation, while group C rats received non-labeled NSCs implantation. After cell implantation, all the rats were performed T2*-weighted magnetic resonance imaging (MRI) scan at day 1, and 1 wk to 4 wk, to track NSCs distribution in rats’ brains. One month after cell implantation, all the rats were performed manganese-enhanced MRI (ME-MRI) scan. In group B, diltiazem was infused during the ME-MRI scan period.
 
 
 
 (1) iPS cells were successfully derived from skin fibroblasts using the 4 classic factors Oct4, Sox2, Myc, and Klf4, expressing the typical antigens including SSEA4, Oct4, Sox2, and Nanog. (2) iPS cells were induced to differentiate into NSCs, which could express Nestin and differentiate into neural cells and glia cells. (3) NSCs were incubated with SPIOs overnight, and prussian blue staining showed intra-cellular particles. (4) After cell implantation, T2*-weighted MRI scan showed these implanted NSCs could migrate to the injury area in chronological order. (5) The subsequent ME-MRI scan detected NSCs function, which could be blocked by diltiazem.
 
 
 
 In conclusion, using in Vivo MRI tracking technique to trace the fate of iPS cells-induced NSCs in host brain is feasible.
