PET Demonstrates Functional Recovery After Transplantation of Induced Pluripotent Stem Cells in a Rat Model of Cerebral Ischemic Injury

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. Methods: 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. Results: 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 celltreated 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. Conclusion: 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.

Small-animal PET demonstrates brain metabolic change after using bevacizumab in a rat model of cerebral ischemic injury

“…2-deoxy-2-18 F-fluoro-D-glucose ( 18 F-FDG), the most extensively used PET imaging tracer, can detect subtle changes of glucose metabolism after stroke [26] . In a previous study, we successfully used 18 F-FDG small-animal PET to evaluate the metabolic recovery of the cerebral infarction in an ischemic stroke model [27] . In this study, we used 18 F-FDG PET to assess the metabolic changes, along with related immunohistochemical and functional changes, in a rat model of cerebral ischemia treated with bevacizumab.…”

“…MCAO was induced as previously described [27] . Briefly, animals were anesthetized intraperitoneally with 1.5%…”

Spatiotemporal PET Imaging of Dynamic Metabolic Changes After Therapeutic Approaches of Induced Pluripotent Stem Cells, Neuronal Stem Cells, and a Chinese Patent Medicine in Stroke

“…Cerebral ischemia-reperfusion injury was induced by the intraluminal suture technique as previously described (19). Reperfusion was performed by withdrawal of the suture 90 min after MCAO (details are provided in the supplemental materials, available at http://jnm.…”

Roles of facilitative glucose transporter GLUT1 in [18F]FDG positron emission tomography (PET) imaging of human diseases

“…product scutellarin [246], the herbal medicine Danhong [247] and after transplantation of induced pluripotent stem cells [248]. In rat brain, GLUT1 overexpression occurs rapidly and widely in microvessels and parenchyma following global cerebral ischemia, which may be associated with an immediate early-gene form of response to cellular stress [249], and cerebral hypoxia-ischemia leads to overexpression of GLUT1 in both damaged and undamaged hemispheres during both early and late stages in the recovery period [250,251].…”