title: 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 (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Fahuan
authors.initials: F
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Zefeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: 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.
authors.lastname: YehuaShen
authors.affiliation: 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.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Yunqi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: 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.
authors.forename: Ruili
authors.initials: R
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Tian
mesh_terms: D000818:Animals; D044466:Asian People; D001345:Autoradiography; D002561:Cerebrovascular Disorders / Q000188:drug therapy / Q000628:therapy; D002681:China; D003131:Combined Modality Therapy; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000000981:diagnostic imaging*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000628:therapy; D008297:Male; D058953:Neural Stem Cells / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D011597:Psychomotor Performance; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000628:therapy; D033581:Stem Cell Transplantation / Q000379:methods*; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D004365:Drugs, Chinese Herbal; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Qing-kai-ling (QKL); induced pluripotent stem cell (iPSC); middle cerebral artery occlusion (MCAO); neuronal stem cell (NSC); positron emission tomography (PET)