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

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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DOI:
10.1007/s00259-019-04408-2
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发表时间:
2019-10-01
影响因子:
9.1
通讯作者:
Tian, Mei
Tian, Mei
中科院分区:
医学1区
文献类型:
--
作者:
Du, Ruili;Zhu, Xiandi;Tian, Mei

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目的干细胞移植是治疗颞叶癫痫(TLE)的有效方法。本研究旨在应用正电子发射计算机断层扫描(PET)技术研究人神经干细胞(NSCs)和人GABA前体细胞(GPC)在TLE大鼠模型移植后的动态代谢变化。方法神经干细胞和GPC移植后进行F-18-FDG PET显像、视频脑电(EEG)、全细胞膜片钳记录和免疫组织化学染色。结果PET显像显示神经干细胞组的糖代谢逐渐改善,而GPC和对照组的糖代谢降低。视频脑电图显示神经干细胞或GPC移植后癫痫发作受到抑制;全细胞膜片钳证实GPC来源细胞的抑制反应增强;免疫染色研究证实移植的NSCs和GPC可以存活、迁移并分化为成熟的神经元亚型。结论F-18-FDG PET显像可作为TLE患者神经干细胞和GPC移植后糖酵解代谢动态变化的一种鉴别诊断方法。全细胞膜片钳为移植干细胞在宿主回路中的功能成熟和整合提供了证据。
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 F-18-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 F-18-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.