神经干细胞在神经系统疾病中的研究应用进展

随着神经干细胞理论的提出,为神经系统疾病的治疗带来了很大的希望。神经干细胞(NSCs)是指自我更新、且具有分化为神经元、星形胶质细胞、少突胶质细胞等多向分化潜能的细胞。当中枢神经系统受到损伤或退行性变时,内源性神经干细胞开始启动神经修复,但受到数量及微环境的影响,作用非常有限。近年,人们采用各种体外培养方法,可以获得一定数量的外源性神经干细胞,在神经干细胞移植治疗各种神经系统疾病,包括缺血性脑卒中、帕金森病、阿尔茨海默病和脊髓损伤等方面做了很多动物及临床前研究。本文综述神经干细胞移植在神经系统疾病治疗中的应用。     

神经干细胞移植研究进展

神经干细胞是指一类具有自我更新能力和多向分化潜能的细胞,能分化成为神经元、星形胶质细胞、少突胶质细胞等众多神经细胞。成年哺乳动物内源性神经再生能力有限,无法弥补因神经疾病而导致的神经细胞缺失,因而,人们开始寻求外源性神经干细胞移植治疗中枢神经系统疾病的可能,在动物模型上开展了大量研究,并建立了多种移植方法。该文就神经干细胞的特性、来源、移植方式、在中枢神经系统疾病中的实验研究进展等作一综述。     

神经干细胞研究进展

神经干细胞(neural stem cells, NSCs)是中枢神经系统中保持分裂和分化潜能的细胞,对它的研究和应用已成为近年来脑科学研究的一个重要领域.神经干细胞体外培养技术的建立提供了对其进行研究的有力手段.目前的研究主要集中于神经干细胞在脑中的起源、分布及在中枢神经系统疾病治疗中的应用等方面.     

神经干细胞--治疗脑神经性疾病的希望(1)

神经干细胞是脑中多潜能的具有自我更新能力的细胞,在特定环境和因子的诱导下能定向分化成不同的神经细胞类型,它为脑损伤修复及神经性疾病的治疗提供了新的途径,因此具有巨大的潜在应用价值和重大理论研究意义。已经发现在成体鸟类、啮齿类、灵长类和人类脑中都存在能产生神经元的神经干细胞。祖先干细胞向不同细胞系的分化受内源性和外源性机制的调制,尽管目前对这种调制的分子机制并不清楚,然而关于对神经干细胞鉴定、分离及对其特性的研究已经获得了很大的进展。     

人胚胎神经干细胞的基础及应用研究进展

神经干细胞是中枢神经系统中具有增殖、自我更新能力以及多种分化潜能的细胞,对它的研究已经成为神经生物学、发育生物学以及脑科学研究的一个热点。随着神经干细胞（特别是胚胎神经干细胞）的分离、培养成功,神经干细胞移植已被尝试用于神经系统损伤等疾病的治疗。但是,关于胚胎神经干细胞的研究尚处于初级阶段,特别是人胚胎神经干细胞的研究、报道还比较少。本文对国内、外近几年来关于人胚胎神经干细胞的基础及应用研究进展作了综述。     

阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响研究进展

阿司匹林是缺血性脑卒中患者急性期治疗药物及卒中再发的二级预防常用药物,骨髓间充质干细胞(BMSCs)移植是治疗缺血性脑血管疾病的新的新兴技术。已证实阿司匹林可抑制骨髓间充质干细胞的增殖及影响骨髓间充质干细胞的分化。本文就阿司匹林对骨髓间充质干细胞移植治疗缺血性脑卒中的影响等进行综述。     

人胚皮层神经干细胞培养方法的探讨(简报)

神经干细胞是一类具有多向分化潜能、自我复制能力,在特定条件诱因下,能够向特定类型神经元或神经胶质细胞分化的未分化或低分化细胞。神经干细胞的研究对于我们阐明神经发生机制,进行神经变性疾病的细胞替代治疗都有重要意义。目前,从人胚组织分离神经干细胞的方法不尽相同,对于大脑皮层神经干细胞的分离,一些学者认为机     

促红细胞生成素对神经干细胞缺氧性损伤保护作用的实验研究

目的观察外源性EPO对神经干细胞缺氧性损伤的保护作用,为缺氧缺血性脑损伤的治疗提供新思路。方法从孕11.5d（E11.5d）大鼠获得神经干细胞,经无血清培养基悬浮培养并传代,对所获细胞的自我增殖、自我更新及其多分化潜能进行检测。取传3代神经干细胞中添加不同剂量的EPO,在5%O2培养箱中培养120h。通过计数干细胞克隆形成率和MTT法检测神经干细胞的增殖情况。于含血清分化培养基中加入不同剂量的EPO,用NSE和GFAP免疫细胞化学染色观察神经干细胞的分化情况。采用AnnexinⅤ-FITC/PI染色,激光扫描共聚焦显微镜观察、检测细胞凋亡率。结果加入EPO后神经干细胞的克隆形成率和MTT检测的OD值显著增高,细胞凋亡率显著下降,NSE阳性细胞的比例明显升高,其作用随剂量增加而增大,50U/ml时作用最大。结论EPO对神经干细胞缺氧性损伤具有明显的保护作用,并可促进神经干细胞向神经元方向分化。EPO的这种作用随剂量增加而增大,50U/ml时达高峰。     

神经干细胞在缺血缺氧性脑病中的治疗前景

过去认为神经元受损伤后难以再生.近年发现神经干细胞(neuralstemcells,NSC)主要存在于胚胎和成熟个体的中枢神经系统(CNS)中,具有增殖和分化的潜能.NSC成为神经学科的热点课题,是神经发育和疾病研究的重要平台,作为新生神经细胞的“种子”,它为治疗缺血缺氧性脑病提供了新策略,尤其是中枢神经细胞的治疗性再生和基因治疗.对NSC的发育、组织学特点、增殖分化的调控及治疗前景进行了阐述.     

神经干细胞的研究现状及运用前景

近年来的研究表明胚胎期和成年期动物的神经组织及人脑中可以分离出神经干细胞.神经干细胞能不断增殖并且具有分化成神经元、星型胶质细胞和少突胶质细胞的能力.神经干细胞的这种特性为中枢神经系统退行性病变和损伤的治疗打下了基础.对神经干细胞的分布、生物学特性、鉴定、增殖与分化及其治疗中枢神经系统疾病中的应用前景进行了综述.     

Biology and clinical application of neural stem cells

Neural stem cells, which exist in various regions of the CNS throughout the mammalian lifespan, can be expanded and induced to differentiate into neurons and glia in vitro and in vivo. Because of these characteristics, there has been increasing interest in the identification and characterization of neural stem cells and neural progenitor cells both for basic developmental biology studies and for therapeutic applications to the damaged brain. Transplantation of neural stem cells or their derivatives into a host brain and the proliferation and differentiation of endogenous stem cells by pharmacological manipulations are potential treatments for many neurodegenerative diseases and brain injuries, such as Parkinson's disease, brain ischemia and spinal cord injury. Continued progress in neural stem cell research is providing a new future for brain repair.     

Cell Therapy for CNS Trauma

Cell therapy plays an important role in multidisciplinary management of the two major forms of central nervous system (CNS) injury, traumatic brain injury and spinal cord injury, which are caused by external physical trauma. Cell therapy for CNS disorders involves the use of cells of neural or non-neural origin to replace, repair, or enhance the function of the damaged nervous system and is usually achieved by transplantation of the cells, which are isolated and may be modified, e.g., by genetic engineering, when it may be referred to as gene therapy. Because the adult brain cells have a limited capacity to migrate to and regenerate at sites of injury, the use of embryonic stem cells that can be differentiated into various cell types as well as the use of neural stem cells has been explored. Preclinical studies and clinical trials are reviewed. Advantages as well as limitations are discussed. Cell therapy is promising for the treatment of CNS injury because it targets multiple mechanisms in a sustained manner. It can provide repair and regeneration of damaged tissues as well as prolonged release of neuroprotective and other therapeutic substances.     

胚胎干细胞向血液干细胞定向分化的研究进展

骨髓移植是目前治疗恶性白血病以及遗传性血液病最有效的方法之一。但是HLA相匹配的骨髓捐献者严重短缺,骨髓造血干细胞（hematopoietic stem cells,HSCs）体外培养困难,在体外修复患者骨髓造血干细胞技术不成熟,这些都大大限制了骨髓移植在临床上的应用。多能性胚胎干细胞（embryonic stem cells,ESCs）具有自我更新能力,在合适的培养条件下分化形成各种血系细胞,是造血干细胞的另一来源。在过去的二十多年里,血发生的研究是干细胞生物学中最为活跃的领域之一。小鼠及人的胚胎干细胞方面的研究最近取得了重大进展。这篇综述总结了近年来从胚胎干细胞获得造血干细胞的成就,以及在安全和技术上的障碍。胚胎干细胞诱导生成可移植性血干细胞的研究能够使我们更好地了解正常和异常造血发生的机制,同时也为造血干细胞的临床应用提供理论和实验依据。     

Wnt信号通路及相关神经因子对神经再生的影响

脑缺血可造成神经元损伤,影响神经功能。有关神经因子可诱导神经干细胞在一定条件下增殖分化成新的神经细胞,这些新的细胞在缺血性脑损伤后参与神经功能的修复。本文详细介绍了Wnt信号通路中相关蛋白的作用机制和Wnt信号通路对神经再生的影响,以及神经源性因子和促神经发生相关因子对于神经发生的影响。     

Regeneration of the central nervous system using endogenous repair mechanisms

Recent advances in developmental and stem cell biology have made regeneration-based therapies feasible as therapeutic strategies for patients with damaged central nervous systems (CNSs), including those with spinal cord injuries, Parkinson disease, or stroke. These strategies can be classified into two approaches: (i) the replenishment of lost neural cells and (ii) the induction of axonal regeneration. The first approach includes the activation of endogenous neural stem cells (NSCs) in the adult CNS and cell transplantation therapy. Endogenous NSCs have been shown to give rise to new neurons after insults, including ischemia, have been sustained; this form of neurogenesis followed by the migration and functional maturation of neuronal cells, as well as the responses of glial cells and the vascular system play crucial roles in endogenous repair mechanisms in damaged CNS tissue. In this review, we will summarize the recent advances in regeneration-based therapeutic approaches using endogenous NSCs, including the results of our own collaborative groups.     

Green fluorescent protein-labeled mapping of neural stem cells migrating towards damaged areas in the adult central nervous system

Neural stem cells, which are clonogenic cells with multilineage differentiation properties from regions of the fetal brain, cortex and hippocampus, are currently considered as powerful candidates for cell replacement therapy in neurodegenerative disorders, such as Parkinson's disease. A key issue is whether stem cells can survive, migrate and differentiate following transplantation into the adult CNS. Here, enhanced green fluorescent protein plasmid electroporation-transfected neural stem cells from the fetal cortex were grafted into the striatum of a rat model of Parkinson's disease. We found most of the grafted cells could survive in the adult parkinsonian rat brain and migrated towards damaged areas, while they moved randomly in the normal brain. Several grafted cells differentiated into neurons.     

Endogenous neurogenesis following ischaemic brain injury: Insights for therapeutic strategies

Ischaemic stroke is among the most common yet most intractable types of central nervous system (CNS) injury in the adult human population. In the acute stages of disease, neurons in the ischaemic lesion rapidly die and other neuronal populations in the ischaemic penumbra are vulnerable to secondary injury. Multiple parallel approaches are being investigated to develop neuroprotective, reparative and regenerative strategies for the treatment of stroke. Accumulating evidence indicates that cerebral ischaemia initiates an endogenous regenerative response within the adult brain that potentiates adult neurogenesis from populations of neural stem and progenitor cells. A major research focus has been to understand the cellular and molecular mechanisms that underlie the potentiation of adult neurogenesis and to appreciate how interventions designed to modulate these processes could enhance neural regeneration in the post-ischaemic brain. In this review, we highlight recent advances over the last 5 years that help unravel the cellular and molecular mechanisms that potentiate endogenous neurogenesis following cerebral ischaemia and are dissecting the functional importance of this regenerative mechanism following brain injury.This article is part of a Directed Issue entitled: Regenerative Medicine: the challenge of translation.     

神经干细胞分离培养方法的介绍

在成体的许多组织中发现了多能干细胞,这些干细胞可以进行自我复制,参与组织的正常修复。神经干细胞在体外能分化为神经元、星形胶质细胞和少突胶质细胞,并具有多向分化潜能。成体神经干细胞和胚胎干细胞都能分化成成体神经系统中的各种神经细胞。神经干细胞具有自我更新能力,因此神经干细胞可以应用于神经损伤或者神经疾病的修复。本文概述了神经干细胞体外分离培养的方法及其生长影响因子。     

神经干细胞在治疗脑损伤中的应用

神经干细胞（neural stem cells,NSCs）是中枢神经系统中既具有自我更新能力又能分化为神经系统各类细胞的细胞群。在体外一定条件下,NSCs能保持增殖能力,经定向诱导能分化为具有成熟神经细胞特征的各类细胞。NSCs移植治疗研究显示,植入的NSCs能分化为移植部位的神经细胞,并融入、整合该部位,重建受损神经网络,在一定程度上缓解病症。近年来,激活体内内源NSCs治疗神经损伤也逐渐得到广泛关注。因此,NSCs在治疗神经损伤中的应用研究已成为当前神经生物学基础理论和临床应用研究的热点。本文简要介绍了最近关于NSCs在治疗脑损伤中的应用研究进展。     

脑挫裂伤致miR-9升高促进神经干细胞分化

目的：探讨颅脑损伤后miR-9表达的变化和对神经干细胞分化和增值的影响,为颅脑损伤后神经功能修复治疗提出新的思路。方法：通过RT-PCR技术检测miR-9在挫裂伤脑组织中的表达情况;培养胚胎来源神经干细胞,并通过免疫荧光鉴定神经干细胞及其分化;转染miR-9后,通过MTT测定神经干细胞的增殖情况,和流式细胞仪检测分化神经元所占比例。结果：miR-9在挫裂伤脑组织中表达显著上升。对神经干细胞过表达miR-9可显著促进细胞增殖,并诱导分化成神经元。结论：脑挫裂伤时miR-9显著升高,并具有着促进神经干细胞增值和诱导分化的作用,可为伤后神经功能修复提供新的治疗方法。