In vivo tracing of superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells transplanted for traumatic brain injury by susceptibility weighted imaging in a rat model

Abstract

Objective: To label rat bone marrow mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide (SPIO) in vitro, and to monitor the survival and location of these labeled BMSCs in a rat model of traumatic brain injury (TBI) by susceptibility weighted imaging (SWI) sequence.

Methods: BMSCs were cultured in vitro and then labeled with SPIO. Totally 24 male Sprague Dawley (SD) rats weighing 200-250 g were randomly divided into 4 groups: Groups A-D (n equal to 6 for each group). Moderate TBI models of all the rats were developed in the left hemisphere following Feeney's method. Group A was the experimental group and stereotaxic transplantation of BMSCs labeled with SPIO into the region nearby the contusion was conducted in this group 24 hours after TBI modeling. The other three groups were control groups with transplantation of SPIO, unlabeled BMSCs and injection of nutrient solution respectively conducted in Groups B, C and D at the same time. Monitoring of these SPIO-labeled BMSCs by SWI was performed one day, one week and three weeks after implantation.

Results: Numerous BMSCs were successfully labeled with SPIO. They were positive for Prussian blue staining and intracytoplasm positive blue stained particles were found under a microscope (200). Scattered little iron particles were observed in the vesicles by electron microscopy (5000). MRI of the transplantation sites of the left hemisphere demonstrated a low signal intensity on magnitude images, phase images and SWI images for all the test rats in Group A, and the lesion in the left parietal cortex demonstrated a semicircular low intensity on SWI images, which clearly showed the distribution and migration of BMSCs in the first and third weeks. For Group B, a low signal intensity by MRI was only observed on the first day but undetected during the following examination. No signals were observed in Groups C and D at any time points.

Conclusion: SWI sequence in vivo can consecutively and noninvasively trace and demonstrate the status and distribution of BMSCs labeled with SPIO in the brain of TBI model rats.