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PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy

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Abstract

Purpose

Stem cell transplantation is promising for temporal lobe epilepsy (TLE) treatment. This study aimed to use PET imaging for the investigation of dynamic metabolic changes after transplantation of human neural stem cells (NSCs) and human GABA progenitor cells (GPCs) in a rat model of TLE.

Methods

18F-FDG PET imaging, video-electroencephalography (EEG), whole-cell patch-clamp recordings and immunostaining were performed after transplantation of NSCs and GPCs.

Results

PET imaging demonstrated that glucose metabolism was gradually improved in the NSCs group, but decreased in GPCs and the control. Video-EEG manifested that seizures were suppressed after NSCs or GPCs transplantation; whole-cell patch-clamp confirmed increased inhibitory response of GPC-derived cells; immunostaining studies verified that the transplanted NSCs and GPCs could survive, migrate and differentiate into mature neuronal subtypes.

Conclusion

18F-FDG PET imaging could be a distinguishing approach for evaluation of dynamic glycolytic metabolic changes after transplantation of NSCs and GPCs in TLE. Whole-cell patch-clamp provides evidence for functional maturation and integration of transplanted stem cells within host circuits.

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Acknowledgements

We thank Qianyun Liu (Hopstem Biotechnology LLC) for technical support on immunostaining, and Prof. Linghui Zeng (Department of Pharmacology, School of Medicine, Zhejiang University City College) for patch-clamp data analysis.

Funding

This study was sponsored by the National Key Research and Development Program of China (2016YFA0100900), National Natural Science Foundation of China (NSFC) (81761148029, 81725009, 81571711, 81425015), and Zhejiang University K.P. Chao’s High Technology Development Foundation.

Author information

Author notes

  1. Ruili Du, Xiandi Zhu, Shuang Wu, Xiaohui Zhang, Yang He and Kai Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine and PET Center, The Second Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China

    Ruili Du, Xiandi Zhu, Shuang Wu, Xiaohui Zhang, Kai Zhang, Xiao He, Hong Zhang & Mei Tian

  2. Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou, China

    Ruili Du, Xiandi Zhu, Shuang Wu, Xiaohui Zhang, Kai Zhang, Xiao He, Hong Zhang & Mei Tian

  3. Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou, China

    Ruili Du, Xiandi Zhu, Shuang Wu, Xiaohui Zhang, Kai Zhang, Xiao He, Hong Zhang & Mei Tian

  4. Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China

    Yang He

  5. Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    Xiaoqun Wang

  6. State Key Laboratory of Membrane Biology, Biodynamic Optical Imaging Center (BIOPIC), Peking University School of Life Sciences, Beijing, China

    Yujie Sun

  7. Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, China

    Qiangbin Wang

Authors
  1. Ruili Du
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  2. Xiandi Zhu
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  3. Shuang Wu
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  4. Xiaohui Zhang
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  5. Yang He
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  6. Kai Zhang
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  7. Xiao He
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  8. Xiaoqun Wang
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  9. Yujie Sun
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  10. Qiangbin Wang
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  11. Hong Zhang
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  12. Mei Tian
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Corresponding authors

Correspondence to Hong Zhang or Mei Tian.

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Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

All experiments were performed following protocols of the Institutional Animal Care and Use Committee (IACUC) of Zhejiang University School of Medicine (Protocol No. #ZJU2015-068-02), under the regulations of the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC International) and National Research Council’s Guide for the Care and Use of Laboratory Animals.

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This article is part of the Topical Collection on Preclinical Imaging

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Du, R., Zhu, X., Wu, S. et al. PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy. Eur J Nucl Med Mol Imaging 46, 2392–2397 (2019). https://doi.org/10.1007/s00259-019-04408-2

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  • DOI: https://doi.org/10.1007/s00259-019-04408-2

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