PET imaging of metabolic changes after neural stem cells and GABA progenitor cells transplantation in a rat model of temporal lobe epilepsy
- 232 Downloads
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.
18F-FDG PET imaging, video-electroencephalography (EEG), whole-cell patch-clamp recordings and immunostaining were performed after transplantation of NSCs and GPCs.
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.
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.
KeywordsTemporal lobe epilepsy (TLE) Glucose metabolism Positron emission tomography (PET) Neural stem cells (NSCs) GABA progenitor cells (GPCs)
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.
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.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
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.
- 3.Upadhya D, Hattiangady B, Castro OW, Shuai B, Kodali M, Attaluri S, et al. Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration. Proc Natl Acad Sci USA. 2019;116(1):287–96.CrossRefPubMedGoogle Scholar
- 4.Miltiadous P, Kouroupi G, Stamatakis A, Koutsoudaki PN, Matsas R, Stylianopoulou F. Subventricular zone-derived neural stem cell grafts protect against hippocampal degeneration and restore cognitive function in the mouse following intrahippocampal kainic acid administration. Stem Cells Transl Med. 2013;2(3):185–98.CrossRefPubMedPubMedCentralGoogle Scholar