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癫痫的干细胞修复策略

Stem cell repair strategies for epilepsy.

作者信息

Ma Xiao, Wang Zitong, Niu Yinuo, Zhao Jie, Wang Xiaorui, Wang Xuan, Yang Fang, Wei Dong, Sun Zhongqing, Jiang Wen

机构信息

Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.

出版信息

Neural Regen Res. 2026 Apr 1;21(4):1428-1446. doi: 10.4103/NRR.NRR-D-24-01337. Epub 2025 Jun 19.


DOI:10.4103/NRR.NRR-D-24-01337
PMID:40537022
Abstract

Epilepsy is a serious neurological disorder; however, the effectiveness of current medications is often suboptimal. Recently, stem cell technology has demonstrated remarkable therapeutic potential in addressing various neurological diseases, igniting interest in its applicability for epilepsy treatment. This comprehensive review summarizes different therapeutic approaches utilizing various types of stem cells. Preclinical experiments have explored the use and potential therapeutic effects of mesenchymal stem cells, including genetically modified variants. Clinical trials involving patient-derived mesenchymal stem cells have shown promising results, with reductions in the frequency of epileptic seizures and improvements in neurological, cognitive, and motor functions reported. Another promising therapeutic strategy involves neural stem cells. These cells can be cultured outside the body and directed to differentiate into specific cell types. The transplant of neural stem cells has the potential to replace lost inhibitory interneurons, providing a novel treatment avenue for epilepsy. Embryonic stem cells are characterized by their significant capacity for self-renewal and their ability to differentiate into any type of somatic cell. In epilepsy treatment, embryonic stem cells can serve three primary functions: neuron regeneration, the maintenance of cellular homeostasis, and restorative activity. One notable strategy involves differentiating embryonic stem cells into γ-aminobutyric acidergic neurons for transplantation into lesion sites. This approach is currently undergoing clinical trials and could be a breakthrough in the treatment of refractory epilepsy. Induced pluripotent stem cells share the same genetic background as the donor, thereby reducing the risk of immune rejection and addressing ethical concerns. However, research on induced pluripotent stem cell therapy remains in the preclinical stage. Despite the promise of stem cell therapies for epilepsy, several limitations must be addressed. Safety concerns persist, including issues such as tumor formation, and the low survival rate of transplanted cells remains a significant challenge. Additionally, the high cost of these treatments may be prohibitive for some patients. In summary, stem cell therapy shows considerable promise in managing epilepsy, but further research is needed to overcome its existing limitations and enhance its clinical applicability.

摘要

癫痫是一种严重的神经系统疾病;然而,目前药物的疗效往往不尽人意。最近,干细胞技术在治疗各种神经系统疾病方面展现出显著的治疗潜力,引发了人们对其在癫痫治疗中适用性的兴趣。这篇综述总结了利用各种类型干细胞的不同治疗方法。临床前实验探索了间充质干细胞的使用及其潜在治疗效果,包括基因改造变体。涉及患者来源间充质干细胞的临床试验已显示出有希望的结果,报告称癫痫发作频率降低,神经、认知和运动功能得到改善。另一种有前景的治疗策略涉及神经干细胞。这些细胞可以在体外培养并定向分化为特定细胞类型。神经干细胞移植有可能替代丢失的抑制性中间神经元,为癫痫提供一种新的治疗途径。胚胎干细胞的特点是具有显著的自我更新能力以及分化为任何类型体细胞的能力。在癫痫治疗中,胚胎干细胞可发挥三种主要功能:神经元再生、维持细胞稳态和恢复活性。一种值得注意的策略是将胚胎干细胞分化为γ-氨基丁酸能神经元以移植到损伤部位。这种方法目前正在进行临床试验,可能成为难治性癫痫治疗的一个突破。诱导多能干细胞与供体具有相同的遗传背景,从而降低了免疫排斥风险并解决了伦理问题。然而,诱导多能干细胞疗法的研究仍处于临床前阶段。尽管干细胞疗法对癫痫治疗有前景,但必须解决几个限制因素。安全问题依然存在,包括肿瘤形成等问题,而且移植细胞的低存活率仍然是一个重大挑战。此外,这些治疗的高成本可能使一些患者望而却步。总之,干细胞疗法在治疗癫痫方面显示出相当大的前景,但需要进一步研究以克服其现有局限性并提高其临床适用性。

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本文引用的文献

[1]
Modeling and correction of protein conformational disease in iPSC-derived neurons through personalized base editing.

Mol Ther Nucleic Acids. 2024-12-21

[2]
Release your inhibitions: The cell biology of GABAergic postsynaptic plasticity.

Curr Opin Neurobiol. 2025-2

[3]
Recent advances in stem cell therapy: efficacy, ethics, safety concerns, and future directions focusing on neurodegenerative disorders - a review.

Int J Surg. 2024-10-1

[4]
Insights and progress on the biosynthesis, metabolism, and physiological functions of gamma-aminobutyric acid (GABA): a review.

PeerJ. 2024-12-16

[5]
A Comprehensive Overview of the Current Status and Advancements in Various Treatment Strategies against Epilepsy.

ACS Pharmacol Transl Sci. 2024-11-1

[6]
Cenobamate, a New Promising Antiseizure Medication: Experimental and Clinical Aspects.

Int J Mol Sci. 2024-12-3

[7]
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Lancet Neurol. 2025-1

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Rev Prat. 2024-11

[9]
Comparative analysis of regulations and studies on stem cell therapies: focusing on induced pluripotent stem cell (iPSC)-based treatments.

Stem Cell Res Ther. 2024-11-21

[10]
Epilepsy-surgery for fronto-basal lesions: Management, outcome, and review of literature.

Seizure. 2024-12

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