神经干细胞、成体神经发生以及神经变性疾病的细胞移植治疗

神经药理学报 ›› 2015, Vol. 5 ›› Issue (3): 46-64.

• 综述 • 上一篇

神经干细胞、成体神经发生以及神经变性疾病的细胞移植治疗

汪伦政，谢文娟，唐铁山

1. 膜生物学国家重点实验室，中国科学院动物研究所，北京，100101，中国
2. 中国科学院大学生命科学学院，北京，100049，中国

出版日期:2015-06-26 发布日期:2015-07-06
通讯作者: 唐铁山，男，研究员，博士生导师；研究方向：分子神经生物学；Tel：+86-10-64807296，E-mail：tangtsh@ioz.ac.cn
作者简介:汪伦政，男，研究生；研究方向：分子神经生物学；E-mail：scodking@qq.com
基金资助:
本研究受到科技部重大科学计划(2011CB965003, 2012CB944702)、国家自然科学基金 (81371415, 31570816, 31401151, 81300982)的资助

Neural Stem Cells, Adult Neurogenesis and Cell Therapy for Neurodegenerative Diseases

WANG Lun-zheng, XIE Wen-juan, TANG Tie-Shan

1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2. University of Chinese Academy of Sciences, Beijing 100049, China

Online:2015-06-26 Published:2015-07-06
Contact: 唐铁山，男，研究员，博士生导师；研究方向：分子神经生物学；Tel：+86-10-64807296，E-mail：tangtsh@ioz.ac.cn
About author:汪伦政，男，研究生；研究方向：分子神经生物学；E-mail：scodking@qq.com
Supported by:
本研究受到科技部重大科学计划(2011CB965003, 2012CB944702)、国家自然科学基金 (81371415, 31570816, 31401151, 81300982)的资助

摘要/Abstract

摘要： 成体哺乳动物的神经元是退出细胞周期的终末分化细胞，因此长期以来神经系统被认为缺乏再生能力。自神经干细胞（neural stem cells，NSCs）及神经发生在许多物种尤其哺乳动物的成体中被广泛发现和证实后，成体中枢神经系统的可塑性和神经发生的机制和功能成为神经科学研究的热点。神经干细胞的基因组在多种表观遗传因子和微环境的共同调节下，在特定时间和空间中表达出特异的RNA及蛋白质。新生神经细胞经过增殖、分化、迁移、整合并最终成熟为特化的神经细胞，这一过程即为成体神经发生。成体哺乳动物脑中的神经发生贯穿整个生命周期，且已在侧脑室的室管膜下区（subventricular zone，SVZ）和海马齿状回（dentate gyrus，DG）的颗粒下区（subgranular zone，SGZ）被明确证实。成体神经发生受到多种生理和病理因素的调控，与嗅球和海马等脑区的功能密切相关。移植神经干细胞治疗中枢神经系统（central nervous system，CNS）变性疾病被广泛研究并且在临床前实验中有明显的治疗效果。然而，成体神经发生的分子机制尚不明确，尤其新生神经细胞如何与CNS的神经细胞、免疫细胞、以及微环境相互作用而发挥治疗作用需要深入研究。此外，神经干细胞移植疗法还需要解决神经干细胞来源、体外培养技术、免疫排斥、移植剂量、脑部定位以及各种疾病治疗的最佳时间窗口选择等问题。总之，深入了解神经干细胞及神经发生的机制不仅会极大地推动神经科学的基础研究，也为CNS相关疾病提供了新的有效的治疗方案，有着广阔的理论和应用前景。

关键词: 神经干细胞, 神经发生, 表观遗传, 中枢神经系统, 细胞移植

Abstract: Neurons in adult mammals are terminally differentiated cells，so the nervous system has long been considered lack of regeneration ability. However，since the adult neural stem cells（ NSCs） and neurogenesis have been widely found and identified in many species，especially in mammals，the plasticity of central nervous system（ CNS） and the mechanisms of the neurogenesis quickly become hotspots in neuroscience. Adult neurogenesis is a process that the neural stem cells express specific RNAs and proteins in specific time and space when their homogeneous genomes are regulated by diverse epigenetic factors and microenvironment，and the novel cells experience proliferation，differentiation，migration，integration and ultimately mature into specialized nerve cells. Adult neurogenesis of mammals has been proven in the subventricular zone（ SVZ） of the lateral ventricle and the subgranular zone（ SGZ） of the dentate gyrus in the hippocampus. Adult neurogenesis is regulated by a variety of physiological and pathological factors and plays a role in the functions of olfactory bulb，hippocampus and other regions of the brain. The approaches for the treatment of CNS diseases by transplanting the NSCs into the abnormal brains have been widely studied，and the preclinical studies show obvious therapeutic effects. Nevertheless，the molecular mechanisms of neurogenesis are not clear during the whole process，especially the therapeutic mechanisms how the new born cells interact with the immune cells，the molecular nets and the microenvironment of the CNS need to be studied deeply. In addition，there is still a long way to go to solve several key problems such as the source of NSCs，NSCs culture technology in vitro，immunological rejection，cell dosage，transplant location and the optimal therapeutic time window for each kind of disease. In short，the studies on the NSCs and neurogenesis will not only promote the development of neuroscience but also provide new therapeutic regimens for the CNS diseases，and thus，have a broad prospect for cell therapy applications.

Key words: neural stem cells, neurogenesis, epigenetic, central nervous system, cell transplantation

中图分类号:

R741

汪伦政，谢文娟，唐铁山. 神经干细胞、成体神经发生以及神经变性疾病的细胞移植治疗[J]. 神经药理学报, 2015, 5(3): 46-64.

WANG Lun-zheng, XIE Wen-juan, TANG Tie-Shan. Neural Stem Cells, Adult Neurogenesis and Cell Therapy for Neurodegenerative Diseases[J]. Acta Neuropharmacologica, 2015, 5(3): 46-64.

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神经干细胞、成体神经发生以及神经变性疾病的细胞移植治疗

Neural Stem Cells, Adult Neurogenesis and Cell Therapy for Neurodegenerative Diseases

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