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

Abstract

This study aimed to use spatiotemporal PET imaging to investigate the dynamic metabolic changes after a combined therapeutic approach of induced pluripotent stem cells (iPSCs), neuronal stem cells (NSCs), and Chinese patent medicine in a rat model of cerebral ischemia-reperfusion injury. Methods: Cerebral ischemia was established by the middle cerebral artery occlusion approach. Thirty-six male rats were randomly assigned to 1 of the 6 groups: control phosphate-buffered saline (PBS), Chinese patent medicine (Qing-kai-ling [QKL]), induced pluripotent stem cells (iPSCs), combination of iPSCs and QKL, neuronal stem cells (NSCs), and combination of NSCs and QKL. Serial 18F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohisto-chemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. Results: Compared with the PBS control group, significantly higher 18F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive 18F-FDG accumulation was found in the NSCs 1 QKL group at week 1 but in the iPSCs 1 QKL group at week 4. The neuro-functional scores in the 5 treatment groups were significantly higher than that of the PBS group from week 3 to 4. In addition, there was a significant correlation between the PET imaging findings and neurofunctional recovery (P < 0.05) or glucose transporter-1 expression (P < 0.01). Immunohistochemical and immunofluorescence studies found that transplanted iPSCs survived and migrated to the ischemic region and expressed protein markers for cells of interest. Conclusion: Spatiotemporal PET imaging with 18F-FDG demonstrated dynamic metabolic and functional recovery after iPSCs or NSCs combined with QKL in a rat model of cerebral ischemia-reperfusion injury. iPSCs or NSCs combined with Chinese medicine QKL seemed to be a better therapeutic approach than these stem cells used individually.