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

Journal of Nuclear Medicine

Caiyun Xu¹  Shuang Wu¹  Mei Tian¹  Ruili Du¹  Yao Chen¹  Zefeng Wang¹  YehuaShen¹  Jinhui Li¹  Hong Zhang¹  Hao Liu¹  Yunqi Zhu¹  Fahuan Song¹ 

[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 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 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

关键词: induced pluripotent stem cell (iPSC);    neuronal stem cell (NSC);    Qing-kai-ling (QKL);    positron emission tomography (PET);    middle cerebral artery occlusion (MCAO);   

DOI  :  10.2967/jnumed.115.163170

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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 immunohistochemical 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 + 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 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.

【 授权许可】

Unknown