Complex partial seizures arising from mesial temporal lobe structures are a defining feature of mesial temporal lobe epilepsy (TLE). For many TLE patients, there is an initial traumatic head injury that is the precipitating cause of epilepsy. Severe TLE can be associated with neuropathological changes, including hippocampal sclerosis, neurodegeneration in the dentate gyrus, and extensive reorganization of hippocampal circuits. Learning disabilities and psychiatric conditions may also occur in patients with severe TLE for whom conventional anti-epileptic drugs are ineffective. Novel treatments are needed to limit or repair neuronal damage, particularly to hippocampus and related limbic regions in severe TLE and to suppress temporal lobe seizures. A promising therapeutic strategy may be to restore inhibition of dentate gyrus granule neurons by means of cell grafts of embryonic stem cell-derived GABAergic neuron precursors. “Proof-of-concept” studies show that human and mouse embryonic stem cell-derived neural precursors can survive, migrate, and integrate into the brains of rodents in different experimental models of TLE. In addition, studies have shown that hippocampal grafts of cell lines engineered to release GABA or other anticonvulsant molecules can suppress seizures. Furthermore, transplants of fetal GABAergic progenitors from the mouse or human brain have also been shown to suppress the development of seizures. Here, we review these relevant studies and highlight areas of future research directed toward producing embryonic stem cell-derived GABAergic interneurons for cell-based therapies for treating TLE.

中文翻译：

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胚胎干细胞衍生的神经前体移植物用于治疗颞叶癫痫。


由内侧颞叶结构引起的复杂部分性癫痫发作是内侧颞叶癫痫（TLE）的一个定义特征。对于许多 TLE 患者来说，最初的头部外伤是癫痫的诱因。严重的 TLE 可能与神经病理变化相关，包括海马硬化、齿状回神经变性和海马回路的广泛重组。传统抗癫痫药物无效的严重 TLE 患者也可能出现学习障碍和精神疾病。需要新的治疗方法来限制或修复神经元损伤，特别是严重 TLE 中的海马和相关边缘区域，并抑制颞叶癫痫发作。一种有前途的治疗策略可能是通过胚胎干细胞衍生的 GABA 能神经元前体的细胞移植来恢复对齿状回颗粒神经元的抑制。 “概念验证”研究表明，人类和小鼠胚胎干细胞衍生的神经前体细胞可以在不同的 TLE 实验模型中存活、迁移并整合到啮齿类动物的大脑中。此外，研究表明，海马移植的细胞系经过改造可以释放 GABA 或其他抗惊厥分子，可以抑制癫痫发作。此外，移植来自小鼠或人脑的胎儿 GABA 能祖细胞也被证明可以抑制癫痫发作。在这里，我们回顾了这些相关研究，并重点介绍了未来的研究领域，旨在生产胚胎干细胞衍生的 GABA 能中间神经元，用于治疗 TLE 的细胞疗法。