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

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.

• Authors: Hong Zhang, Fahuan Song, Caiyun Xu, Hao Liu, Zefeng Wang, Jinhui Li, Shuang Wu, YehuaShen, Yao Chen, Yunqi Zhu, Ruili Du, Mei Tian
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 56 Issue 11 Pg. 1774-9 (Nov 2015) ISSN: 1535-5667 [Electronic] United States
• PMID: 26359258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Drugs, Chinese Herbal
• Radiopharmaceuticals
• Fluorodeoxyglucose F18

Topics

• Animals
• Asian People
• Autoradiography
• Cerebrovascular Disorders (drug therapy, 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, therapy)
• Male
• Neural Stem Cells (diagnostic imaging)
• Positron-Emission Tomography (methods)
• Psychomotor Performance
• Radiopharmaceuticals (pharmacokinetics)
• Rats
• Reperfusion Injury (drug therapy, therapy)
• Stem Cell Transplantation (methods)
• Stroke (diagnostic imaging, drug therapy, therapy)
• Treatment Outcome