Hong Zhang1, Fahuan Song1, Caiyun Xu1, Hao Liu1, Zefeng Wang1, Jinhui Li1, Shuang Wu1, Yao Chen1, Yunqi Zhu1, Ruili Du1, Mei Tian2. 1. Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Zhejiang University Medical PET Center, Zhejiang University, Hangzhou, China; Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China; and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China. 2. Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China; Zhejiang University Medical PET Center, Zhejiang University, Hangzhou, China; Institute of Nuclear Medicine and Molecular Imaging, Zhejiang University, Hangzhou, China; Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China; and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, China meitian@zju.edu.cn.
Abstract
UNLABELLED: 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 (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. RESULTS: Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional 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 (18)F-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.
UNLABELLED: 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 (18)F-FDG small-animal PET imaging and neurofunctional tests were performed weekly. Autoradiographic imaging and immunohistochemical and immunofluorescent analyses were performed at 4 wk after stem cell transplantation. RESULTS: Compared with the PBS control group, significantly higher (18)F-FDG accumulations in the ipsilateral cerebral infarction were observed in 5 treatment groups from weeks 1-4. Interestingly, the most intensive (18)F-FDG accumulation was found in the NSCs + QKL group at week 1 but in the iPSCs + QKL group at week 4. The neurofunctional 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 (18)F-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.