Labeling neural stem cells with superparamagnetic iron oxide and MRI tracking in vitro and in vivo

Objective: To label neural stem cells with superparamagnetic iron oxide (SPIO) and track labeled cells with MRI in vitro and in vivo after implantation. Methods: 13 SD rats were used for the study. Rat neural stem cells were labeled with SPIO combined with PLL by the mean of receptor-mediated endocytosis. Prussian blue staining and electron microscopy were conducted to identify the iron particles in these neural stem cells, and SPIO-labeled cells were tracked with 1.5 T and 4.7T MRI in vivo and in vitro after implantation. The subjects were divided into five groups, including 5 x l05 labeled cells, 5 x l05 unlabeled cells, cell culture medium with SPIO, cell culture medium without SPIO and distilled water. MRI scanning sequences included T1WI, T2WI and T2* WI. R2 and R2* relaxation rate of labeled cells were calculated. Results: (1) Neural stem cells could be labeled with SPIO and labeling efficiency was 100%, Prussian blue staining showed numerous blue-stained iron particles in the cytoplasm. (2) The average percentage change of signal intensity of labeled cells on T1WI in 1.5 T and 4.7 T MRI was 20.53% and 24.06% respectively, on T2WI was 40.78% and 50.66% respectively, and on T2* WI was 46.57% and 53.70% respectively. The signal intensity had no significant difference between T2WI and T2* WI in 1.5 T MRI, however the signal intensity had significant difference between T2WI or T2* WI and T1WI. (3) T2 of unlabeled cells and labeled cells in 4.7 T MRI were 516 ms and 77 ms respectively, R2 were 1.94 s-1 and 12.98 s-1 respectively; and T2* were 109 ms and 22.9 ms, R2* were 9.17 s-1 and 43.67 s-1 respectively. (4) Remarkable low signal area on T2WI and T2* WI was seen in the left brain implanted with labeled cells one week ago, however no signal change in the right brain implanted with unlabeled cells. Conclusion: Neural stem cells can be labeled effectively with SPIO; R2 and R2* of labeled cells were increased obviously; MRI can be used to track labeled cells in vitro and in vivo. (authors)