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.     

神经干细胞迁移浅识

神经干细胞的迁移是近年来神经科学领域研究的热点之一.神经干细胞的增殖、迁移、分化和网络重建的特性为研究中枢神经系统退行性疾病及损伤后功能的恢复奠定了基础,其中神经干细胞的迁移发挥了重要作用.目前已经有大量研究探索神经干细胞的迁移,本文将分别从神经干细胞的迁移现象、神经干细胞迁移的影响因素及其应用意义等方面做一综述.     

水凝胶理化特性调控神经干细胞命运和神经损伤修复的研究进展

水凝胶(hydrogel)是一类极为亲水的高分子材料,可模拟体内神经干细胞所处的细胞外微环境,作为神经干细胞的载体用于干细胞移植疗法。优化水凝胶的理化特性有利于促进移植的神经干细胞的存活、分化和迁移。水凝胶的理化特性包括基质成分、黏弹性、硬度、降解性、导电性以及水凝胶对物理刺激的响应等。该文综述了水凝胶的不同理化特性对神经干细胞命运的影响和水凝胶结合的神经干细胞在中枢神经系统修复中的应用,为通过调节水凝胶理化特性促进中枢神经系统修复提供线索和见解。     

新生鼠中枢神经系统内Nestin蛋白免疫阳性的组织分布

为了观察Nestin在新生SD大鼠中枢神经系统中的分布,探讨神经干细胞在新生鼠的分布.采用免疫荧光法,显示含神经干细胞特征性的标志物Nestin的阳性结构在新生SD大鼠中枢神经系统中的分布.结果表明在新生SD大鼠中枢神经系统中,Nestin在前脑、脑干和小脑的各个部位均有表达,阳性结构多为纤细的纤维状突起,分布密集,标记强度多为中等强度,分布相对比较均匀.在脊髓实质的Nestin免疫阳性产物明显减少,分布稀疏,染色也较浅,中央管Nestin免疫染色阳性的室管膜细胞很少,但在脊髓中央管的背侧(延髓见于腹侧和背侧)可见到“喷泉”状免疫强阳性纤维束垂直伸展,直达软膜.由此可得出结论:新生SD大鼠中枢神经系统的广泛脑区均存在大量的神经干细胞,而脊髓的神经干细胞数目较少,提示神经干细胞在生后从神经系统的尾端开始逐渐减少.     

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。     

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。     

对比不同类型干细胞对于缺血性脑卒中治疗的研究进展

成人中枢神经系统存在着一定量的神经干细胞,其具有两大关键能力;自我更新和多向分化潜能。缺血性脑卒中是一种由于由脑血流的缺失或减少引起的脑动脉闭塞,进而导致脑组织梗死的脑血管疾病。虽然对于脑损伤的药物治疗已经取得了一定的成果,但目前以干细胞为基础的治疗方法仍成为了研究热点。无论是内源性神经干细胞还是外源性神经干细胞移植均可在脑损伤后向远端损伤区迁移并分化成新的神经细胞,从而在中枢神经系统疾病尤其是脑梗死后进行组织修复和功能恢复。因此在这篇综述中,我们主要探讨不同类型的干细胞对脑梗死介导的脑损伤的应用潜能,对比不同类型干细胞对缺血性脑卒中的治疗优缺点。     

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。     

果蝇神经干细胞研究进展

中枢神经系统由数量庞大、类型多样的神经细胞和神经胶质细胞组成,它调节生物体各种生理活动以及学习、记忆和思维等认知功能。神经细胞和神经胶质细胞由神经干细胞产生,所以对神经干细胞的研究有十分重要的意义。果蝇作为一种经典模式生物,长期被用于神经干细胞增殖、分化、凋亡等方面的研究。本文阐述了果蝇神经干细胞的最新研究进展,包括神经干细胞的类型和起源,参与神经干细胞不对称分裂的关键蛋白质,神经干细胞的静息、激活和最终的分化或凋亡,以及神经元多样性产生的机制,希望对神经生物学的基础研究有所帮助。     

神经干细胞和祖细胞

近年来利用细胞培养技术分离的神经干细胞和祖细胞为研究神经发育提供了一条新的途径,研究神经干细胞和祖细胞的增殖、迁移和分化将为阐明神经发育机制提供有力的证据。同时,神经干细胞还为治疗中枢退行性疾病带来了希望。无论是作为脑组织移植的供体,还是作为在体诱导的靶细胞,神经干细胞都为中枢神经系统功能重建和神经再生提供了新的思路。     

Neural Stem Cells Enhance Nerve Regeneration after Sciatic Nerve Injury in Rats

With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5?×?10⁵ NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.     

Tissue engineered, guided nerve tube consisting of aligned neural stem cells and astrocytes

Injury of the nervous system, particularly in the spinal cord, impairs the quality of life of the patient by resulting in permanent loss of neurologic function. The main limitation in spinal cord regeneration is the lack of extracellular matrix to guide nerves for functional recovery of the transected nerve tissue. In the present study, a tissue engineered nerve tube was prepared by wrapping neural stem cells (NSCs) on aligned fibers using a micropatterned film with astrocytes aligned along the microgrooves to support the NSCs. Initially the cell behavior on micropatterns and parallel fibers was investigated with cytoskeletal and nuclear staining, immunocytochemistry, and proliferation assay using the fiber and the film system separately. The results showed that both cells, NSCs in undifferentiated and astrocytes in differentiated form, were oriented in the direction of the guiding and support elements, the microgrooves, and the microfibers. They were able to grow and increase in number on these cell carriers. This trend was also maintained after the components were brought together in a nerve tube form and testing in coculture. The cells were able to survive and maintained their orientation in the 3D tissue engineered construct. The guided nerve tissue engineering approach tested in the present study with parallel NSCs and support cells in the tubular construct is expected to provide an appropriate environment for nerve regeneration in vivo.     

神经干细胞迁移的研究进展

神经干细胞的定向迁移是胚胎神经系统发育的先决条件,同时在成体组织的许多生理、病理过程中也起着重要作用;研究发现,许多神经退行性疾病都与神经干细胞迁移的缺陷相关。近年来,越来越多的证据表明,无论是内源性的还是移植的神经干细胞都有向大脑损伤部位迁移的特性,显示出神经干细胞用于神经再生及损伤修复治疗的潜能。该文着重在神经干细胞的基本特性以及神经干细胞定向迁移的细胞与分子机制研究等方面进行了综述。     

Optic nerve input‐dependent regulation of neural stem cell proliferation in the optic tectum of adult zebrafish

Adult neurogenesis attracts broad attention as a possible cure for neurological disorders. However, its regulatory mechanism is still unclear. Therefore, they have been studying the cell proliferation mechanisms of neural stem cells (NSCs) using zebrafish, which have high regenerative potential in the adult brain. The presence of neuroepithelial‐type NSCs in the optic tectum of adult zebrafish has been previously reported. In the present study, it was first confirmed that NSCs in the optic tectum decrease or increase in proportion to projection of the optic nerves from the retina. At 4 days after optic nerve crush (ONC), BrdU‐positive cells decreased in the optic tectum's operation side. In contrast, at 3 weeks after ONC, BrdU‐positive cells increased in the optic tectum's operation side. To study the regulatory mechanisms, they focused on the BDNF/TrkB system as a regulatory factor in the ONC model. It was found that bdnf was mainly expressed in the periventricular gray zone (PGZ) of the optic tectum by using in situ hybridization. Interestingly, expression level of bdnf significantly decreased in the optic tectum at 4 days after ONC, and its expression level tended to increase at 3 weeks after ONC. They conducted rescue experiments using a TrkB agonist and confirmed that decrease of NSC proliferation in the optic tectum by ONC was rescued by TrkB signal activation, suggesting stimuli‐dependent regulation of NSC proliferation in the optic tectum of adult zebrafish. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419–437, 2017     

TAM Receptors Support Neural Stem Cell Survival,Proliferation and Neuronal Differentiation

Tyro3, Axl and Mertk (TAM) receptor tyrosine kinases play multiple functional roles by either providing intrinsic trophic support for cell growth or regulating the expression of target genes that are important in the homeostatic regulation of immune responses. TAM receptors have been shown to regulate adult hippocampal neurogenesis by negatively regulation of glial cell activation in central nervous system (CNS). In the present study, we further demonstrated that all three TAM receptors were expressed by cultured primary neural stem cells (NSCs) and played a direct growth trophic role in NSCs proliferation, neuronal differentiation and survival. The cultured primary NSCs lacking TAM receptors exhibited slower growth, reduced proliferation and increased apoptosis as shown by decreased BrdU incorporation and increased TUNEL labeling, than those from the WT NSCs. In addition, the neuronal differentiation and maturation of the mutant NSCs were impeded, as characterized by less neuronal differentiation (β-tubulin III⁺) and neurite outgrowth than their WT counterparts. To elucidate the underlying mechanism that the TAM receptors play on the differentiating NSCs, we examined the expression profile of neurotrophins and their receptors by real-time qPCR on the total RNAs from hippocampus and primary NSCs; and found that the TKO NSC showed a significant reduction in the expression of both nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), but accompanied by compensational increases in the expression of the TrkA, TrkB, TrkC and p75 receptors. These results suggest that TAM receptors support NSCs survival, proliferation and differentiation by regulating expression of neurotrophins, especially the NGF.     

热带次生林不同林层植物叶片非结构性碳水化合物的季节变化及其对氮磷添加的响应

非结构性碳水化合物(Non-structural Carbohydrates, NSCs)是植物生长代谢过程中重要的能量来源。通过在华南热带次生林进行氮磷添加试验,探究不同林层植物叶片NSCs的季节变化及其对氮磷添加的响应,取样时间为2019年1月、4月、7月和10月。结果表明:1)植物叶片NSCs存在显著的种间差异,磷(P)添加对叶片淀粉和NSCs含量具有显著影响,且物种与磷添加的交互作用显著影响叶片淀粉含量。2)黑嘴蒲桃和紫玉盘叶片NSCs含量对氮(N)添加的响应较为敏感,而白车和竹节叶片NSCs含量对P添加的响应较为敏感,氮磷同时添加(+NP)对植物叶片NSCs的增效作用最好。3)植物叶片NSCs存在显著的季节性变化,且季节与林层间的交互作用对叶片可溶性糖和NSCs含量具有显著影响。4)不同林层植物对氮磷添加的响应不同,氮磷添加使林下层植物叶片可溶性糖含量增高,林冠层降低,在干季,N添加会使林下层植物叶片淀粉含量增高,林冠层降低。P添加的影响恰好与之相反。在湿季,氮磷添加使林下层和林冠层植物叶片的淀粉含量增加。5)林冠层植物叶片NSCs含量高于林下层,且林下层植物叶片NSCs含量...     

Neural stem cell therapy for brain disease

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovascular diseases, and traumatic brain injuries, are among the major disorders influencing human health, currently with no effective therapy. Due to the low regeneration capacity of neurons, insufficient secretion of neurotrophic factors, and the aggravation of ischemia and hypoxia after nerve injury, irreversible loss of functional neurons and nerve tissue damage occurs. This damage is difficult to repair and regenerate the central nervous system after injury. Neural stem cells (NSCs) are pluripotent stem cells that only exist in the central nervous system. They have good self-renewal potential and ability to differentiate into neurons, astrocytes, and oligodendrocytes and improve the cellular microenvironment. NSC transplantation approaches have been made for various neurodegenerative disorders based on their regenerative potential. This review summarizes and discusses the characteristics of NSCs, and the advantages and effects of NSCs in the treatment of brain diseases and limitations of NSC transplantation that need to be addressed for the treatment of brain diseases in the future.     

The alteration of H4-K16ac and H3-K27met influences the differentiation of neural stem cells

The neural stem cell therapy provides a promising future for patients with central nerve system damage, thus an insight into its differentiation mechanism is urgently needed. Herein, we aimed to identify various histone modifications and reveal their impact on the differentiation of neural stem cells (NSCs) toward neurons. Firstly, we labeled primary NSCs using the stable isotope labeling with amino acids in cell culture (SILAC) technique. Then we induced these NSCs to differentiate by all-trans retinoic acid (atRA) or SB216763. Next, we identified the alteration of histone modifications in early-differentiated NSCs by mass spectrometry and verified them by Western blot. Interestingly, these modification alterations and phenotype changes were found similar in NSCs induced by the two different drugs. More interestingly, during the differentiation process H3-K27met was significantly up-regulated while H4-K16ac was not altered at the global level but down-regulated in some low-abundance combinatorial codes. We inhibited the methyltransferase of H3-K27 and deacetylase of H4-K16 simultaneously and found the differentiation procedure was obviously delayed. The function of H4-K16ac and H3-K27met in NSCs differentiation would be useful to reveal the differentiation mechanism and valuable for further neural stem cell therapy.     

Lithium chloride promotes proliferation of neural stem cells in vitro,possibly by triggering the Wnt signaling pathway

The objective of this study was to clarify the relationship between the effect and associated mechanisms of lithium chloride on neural stem cells (NSCs) and the Wnt signaling pathway. The expression of key molecules proteins related to the Wnt signaling pathway in the proliferation and differentiation of control NSCs and lithium chloride-treated NSCs was detected by Western blot analysis. Flow cytometry analysis was applied to study the cell cycle dynamics of control NSCs and NSCs treated with lithium chloride. The therapeutic concentrations of lithium chloride stimulated NSC proliferation. β-catenin expression gradually decreased, while Gsk-3β expression gradually increased (P?P?in vitro and preventing the cells from differentiating, which is potentially mediated by activation of the Wnt signaling pathway.     

Osteogenic and neurogenic differentiation of EGFP gene transfected neural stem cells derived from the brain of porcine fetuses at intermediate and late gestational age

The aims of this study were (i) to determine whether NSCs (neural stem cells) could be isolated from the brain of porcine fetuses at intermediate and late gestational age and (ii) to determine if these stem cells could be differentiated in vitro into osteogenic and neurogenic lineages following transfection with a reporter gene, EGFP (enhanced green fluorescence protein). The NSCs were isolated from the brains of porcine fetuses at intermediate and late gestational age and transfected with EGFP gene using lipofection. The transfected NSCs cells were induced to differentiate into cells of osteogenic and neurogenic lineages. Markers associated with NSCs and their osteogenic and neurogenic derivatives were tested by PCR. The results demonstrated that NSCs could be isolated from the brain of porcine fetus at intermediate and late gestational age and that transfected NSCs expressed EGFP and could be induced to differentiate in vitro. NSCs expressed CD‐90, Hes1, Oct4, Sox2 and Nestin, while following differentiation cells expressed markers for osteogenic (osteocalcin and osteonectin) and neurogenic cells such as astrocyte [GFAP (glial fibrillary acidic protein)], oligodendrocyte [GALC (galactosylceramide)] and neuron [NF (neurofilament), ENO2 (enolase 2) and MAP (microtubule‐associated protein)].