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据报道，美国大约有340万癫痫症患者，尽管大多数患者对药物治疗有反应，但是仍有20%-40%患者在尝试了多种抗癫痫药物后依然发作。此外，即使现有药物发挥了治疗作用，也可能令患者产生认知和记忆障碍以及抑郁。 近日，来自德州A&M大学医学院的Ashok K. Shetty教授课题组研究发现，利用干细胞产生的神经元或能抑制癫痫，并改善癫痫患者认知功能。癫痫发作的病因是大脑中兴奋性神经元放电过量，抑制性神经元数量不足。大脑中主要的抑制性神经元递质为γ-氨基丁酸（GABA）。此前，科学家们已经掌握了如何利用普通成熟体细胞，如皮肤细胞产生诱导多能干细胞，这些干细胞可以分化成多种细胞类型，包括GABA能中间神经元（GABAergic interneurons）。在这项研究中，研究人员在早期颞叶癫痫动物模型中，将人类诱导多能干细胞来源的GABA能祖细胞移植入海马，发现这对抑制癫痫发作、甚至改善动物认知和情绪功能非常有效。进一步测试表明，移植的人类神经元与宿主的兴奋性神经元形成突触或连接，它们对GABA等抑制性中间神经元特殊标记物呈阳性。另一个有趣的发现是，植入的人GABA能神经元似乎直接参与控制癫痫发作，沉默这些神经元则导致癫痫发作次数增加。 研究人员表示，该研究结果对于治疗癫痫这种大脑疾病具有重要的启发意义，干细胞来源的自体神经元移植不会受到排斥，患者也就可能不需要服用抗排斥药物。接下来，研究人员将进一步开展实验以确保所有移植细胞都变成了神经元，避免未分化的多能干细胞在体内造成安全隐患。
推荐阅读原文：
Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration.
Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE. Graft-derived cells survived well, extensively migrated into different subfields of the hippocampus, and differentiated into distinct subclasses of inhibitory interneurons expressing various calcium-binding proteins and neuropeptides. Moreover, grafting of hiPSC-MGE cells after SE mediated several neuroprotective and antiepileptogenic effects in the host hippocampus, as evidenced by reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting in the dentate gyrus (DG). Furthermore, axons from graft-derived interneurons made synapses on the dendrites of host excitatory neurons in the DG and the CA1 subfield of the hippocampus, implying an excellent graft-host synaptic integration. Remarkably, seizure-suppressing effects of grafts were significantly reduced when the activity of graft-derived interneurons was silenced by a designer drug while using donor hiPSC-MGE cells expressing designer receptors exclusively activated by designer drugs (DREADDs). These results implied the direct involvement of graft-derived interneurons in seizure control likely through enhanced inhibitory synaptic transmission. Collectively, the results support a patient-specific MGE cell grafting approach for treating TLE.
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