基因工程骨髓间充质干细胞改善癫痫大鼠模型的功能预后。
Genetically engineered bone marrow mesenchymal stem cells improve functional outcome in a rat model of epilepsy.
机构信息
Department of Neurosurgery, The Central Hospital of Xi'an, Affiliated Hospital of Medical College of Xi'an Jiao Tong University, No. 185 Houzai Gate of North Street, Xi'an 710003, China; Xijing Institute of Clinical Neuroscience, Fourth Military Medical University, No. 17 Chang-le West Road, Xi'an 710032, China.
出版信息
Brain Res. 2013 Sep 26;1532:1-13. doi: 10.1016/j.brainres.2013.07.020. Epub 2013 Aug 6.
Bone marrow mesenchymal stem cells (BMSCs) hold a great promising approach for the treatment of epilepsy owing to their distinctive characteristics and multi-potency. However, there is little research focusing on the multi-potency of BMSCs in the treatment of epilepsy, the present study was designed to examine the influence of genetically engineered BMSCs (GE-BMSCs) on the functional outcome in a rat model of epilepsy. First, Hes1 gene of BMSCs was genetically engineered by RNA interference (RNAi), and then the GABAergic differentiation of GE-BMSCs was tested in vitro. Second, the lithium chloride-pilocarpine induced epileptic rats were administrated with the GE-BMSCs, the behavioral observation and electroencephalography (EEG) monitoring was employed to analyze the functional outcome on the epileptic model at different time points (day 7, day 14, day 21 and day 28), followed by histological verification. In vitro test showed that Hes1 silencing could promote BMSCs to differentiate into GABAergic neuron-like cells. In vivo test showed that GE-BMSCs graft could further improve the functional recovery of the epileptic rats, and the GABAergic differentiation of grafted GE-BMSCs was correlated with the functional recovery. Taken together, these data suggest that GE-BMSCs can improve the functional outcome in a rat model of epilepsy.
骨髓间充质干细胞（BMSCs）因其独特的特性和多能性，为治疗癫痫提供了一种很有前途的方法。然而，目前很少有研究关注 BMSCs 的多能性在癫痫治疗中的作用，本研究旨在探讨基因工程 BMSCs（GE-BMSCs）对癫痫大鼠模型功能结果的影响。首先，通过 RNA 干扰（RNAi）对 BMSCs 的 Hes1 基因进行基因工程改造，然后在体外测试 GE-BMSCs 的 GABA 能分化。其次，将氯化锂-匹罗卡品诱导的癫痫大鼠给予 GE-BMSCs，在不同时间点（第 7 天、第 14 天、第 21 天和第 28 天）通过行为观察和脑电图（EEG）监测分析对癫痫模型的功能结果，并进行组织学验证。体外试验表明，Hes1 沉默可促进 BMSCs 分化为 GABA 能神经元样细胞。体内试验表明，GE-BMSCs 移植可进一步改善癫痫大鼠的功能恢复，移植的 GE-BMSCs 的 GABA 能分化与功能恢复相关。综上所述，这些数据表明 GE-BMSCs 可以改善癫痫大鼠模型的功能结果。
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