據(jù)報道，美國大約有340萬癲癇癥患者，盡管大多數(shù)患者對藥物治療有反應(yīng)，但是仍有20%-40%患者在嘗試了多種抗癲癇藥物后依然發(fā)作。此外，即使現(xiàn)有藥物發(fā)揮了治療作用，也可能令患者產(chǎn)生認(rèn)知和記憶障礙以及抑郁。

近日，來自德州A&M大學(xué)醫(yī)學(xué)院的Ashok K. Shetty教授課題組研究發(fā)現(xiàn)，利用干細(xì)胞產(chǎn)生的神經(jīng)元或能抑制癲癇，并改善癲癇患者認(rèn)知功能。癲癇發(fā)作的病因是大腦中興奮性神經(jīng)元放電過量，抑制性神經(jīng)元數(shù)量不足。大腦中主要的抑制性神經(jīng)元遞質(zhì)為γ-氨基丁酸（GABA）。此前，科學(xué)家們已經(jīng)掌握了如何利用普通成熟體細(xì)胞，如皮膚細(xì)胞產(chǎn)生誘導(dǎo)多能干細(xì)胞，這些干細(xì)胞可以分化成多種細(xì)胞類型，包括GABA能中間神經(jīng)元（GABAergic interneurons）。在這項(xiàng)研究中，研究人員在早期顳葉癲癇動物模型中，將人類誘導(dǎo)多能干細(xì)胞來源的GABA能祖細(xì)胞移植入海馬，發(fā)現(xiàn)這對抑制癲癇發(fā)作、甚至改善動物認(rèn)知和情緒功能非常有效。進(jìn)一步測試表明，移植的人類神經(jīng)元與宿主的興奮性神經(jīng)元形成突觸或連接，它們對GABA等抑制性中間神經(jīng)元特殊標(biāo)記物呈陽性。另一個有趣的發(fā)現(xiàn)是，植入的人GABA能神經(jīng)元似乎直接參與控制癲癇發(fā)作，沉默這些神經(jīng)元則導(dǎo)致癲癇發(fā)作次數(shù)增加。

研究人員表示，該研究結(jié)果對于治療癲癇這種大腦疾病具有重要的啟發(fā)意義，干細(xì)胞來源的自體神經(jīng)元移植不會受到排斥，患者也就可能不需要服用抗排斥藥物。接下來，研究人員將進(jìn)一步開展實(shí)驗(yàn)以確保所有移植細(xì)胞都變成了神經(jīng)元，避免未分化的多能干細(xì)胞在體內(nèi)造成安全隱患。

推薦閱讀原文：
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.