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

J Nucl Med. 2015 Nov;56(11):1774-9. doi: 10.2967/jnumed.115.163170. Epub 2015 Sep 10.

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.

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asian People
  • Autoradiography
  • Cerebrovascular Disorders / drug therapy
  • Cerebrovascular Disorders / therapy
  • China
  • Combined Modality Therapy
  • Drugs, Chinese Herbal / therapeutic use*
  • Fluorodeoxyglucose F18 / pharmacokinetics
  • Humans
  • Induced Pluripotent Stem Cells / diagnostic imaging*
  • Infarction, Middle Cerebral Artery / drug therapy
  • Infarction, Middle Cerebral Artery / therapy
  • Male
  • Neural Stem Cells / diagnostic imaging*
  • Positron-Emission Tomography / methods*
  • Psychomotor Performance
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / therapy
  • Stem Cell Transplantation / methods*
  • Stroke / diagnostic imaging*
  • Stroke / drug therapy
  • Stroke / therapy*
  • Treatment Outcome

Substances

  • Drugs, Chinese Herbal
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18