Abstract
The purpose of this study was to determine the functionality of the transplanted induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) in a rat model of cerebral ischemia with use of (18)F-FDG small-animal PET imaging. Middle cerebral artery occlusion was used to establish cerebral ischemia. Twenty-four male rats were randomly assigned to 1 of 3 groups: iPSC treatment, ESC treatment, and the control phosphate-buffered saline (PBS) injection. After neurologic function tests and baseline (18)F-FDG small-animal PET had been performed, 1.0 × 10(6) suspended iPSCs or ESCs were injected stereotactically into the left lateral ventricle. The treatment response was evaluated weekly by (18)F-FDG PET scans and neurologic function tests. Histologic analyses and autoradiographic imaging were performed 4 wk after stem cell transplantation. Compared with the PBS injection group, higher (18)F-FDG accumulation in the ipsilateral cerebral infarction was observed in both the iPSC and the ESC treatment groups during the 4-wk period (P < 0.05). (18)F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in the iPSC treatment group. At 1 and 2 wk after stem cell transplantation, significant recovery of glucose metabolism was found in the ESC treatment group (P < 0.05) and then decreased gradually. The neurologic score in both stem cell-treated groups was significantly lower than that in the PBS group, indicating functional improvement. Immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated close to the ischemic region, and most of the stem cells expressed protein markers for cells of interest. (18)F-FDG small-animal PET demonstrated metabolic recovery after iPSC and ESC transplantation in the rat model of cerebral ischemia. iPSCs could be considered a potentially better therapeutic approach than ESCs and are worthy of further translational investigation.
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