干细胞植入缺血大脑后功能研究进展

目前,干细胞移植在多个中枢神经系统疾病的研究和临床应用中取得突破性进展。其中,干细胞移植治疗脑缺血疾病是细胞移植治疗研究中最活跃的领域。但是,移植细胞是否具有神经元的功能及细胞移植治疗的机制目前存在很多争议。本文就干细胞移植治疗缺血性脑疾病后移植细胞的功能和治疗缺血性脑疾病机制的可能途径的研究情况作一综述。     

成年鼠脑中神经干细胞的纯化

神经干细胞具有自我复制和多向分化的潜能 ,它可分化为成熟神经元和神经胶质细胞 ,人们希望利用神经干细胞的分化潜能治疗帕金森病等神经系统疾病 ,但首先必须分离纯化这些细胞。以往 ,人们从发育外周神经系统中纯化神经干细胞 ,而脑中干细胞纯化率从未超过 5 %。最近 ,ＲｏｄｎｅｙＬ .Ｒｉｅｔｚｅ等以 80 %的纯化率分离成年鼠脑干细胞并检测这些细胞的特性。他们发现 ,其中一种可在室管膜和脑室下腔区域找到的干细胞活性很强 ,在 ｑｕｅｒｋｏｐｆ变异鼠 (一种嗅觉神经元缺陷的鼠 )中 ,这种细胞选择性缺失 ,提示它可能是离体主要的功能性…     

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。     

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。     

干细胞植入缺血大脑后功能研究进展

目前,干细胞移植在多个中枢神经系统疾病的研究和临床应用中取得突破性进展。其中,干细胞移植治疗脑缺血疾病是细胞移植治疗研究中最活跃的领域。但是,移植细胞是否具有神经元的功能及细胞移植治疗的机制目前存在很多争议。本文就干细胞移植治疗缺血性脑疾病后移植细胞的功能和治疗缺血性脑疾病机制的可能途径的研究情况作一综述。     

诱导多能干细胞在帕金森病治疗中的应用进展

帕金森病（Parkinson's disease, PD）是由于黑质中多巴胺能神经元（dopaminergic neurons, DAns）的病变导致多巴胺含量降低而引起的一种神经退行性疾病,其发病机制尚不明确,而且临床缺乏有效的早期诊断和治疗手段。诱导多能干细胞（induced pluripotent stem cells, iPSCs）的出现为神经系统疾病特别是神经退行性疾病的治疗带来了希望。基于iPSCs的细胞模型可以广泛开展PD发病机制的研究,同时以iPSCs来源的DAns、神经干细胞（neural stem cells, NSCs）等的细胞移植治疗,更是未来PD治疗最有希望的手段。从基于iPSCs的不同基因突变类型的细胞模型与不同分化程度的细胞移植治疗两个方面介绍诱导多能干细胞在PD研究中的进展,旨在分析诱导多能干细胞在帕金森病方面的应用及不足。     

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。     

大鼠胚胎神经干细胞纹状体内移植后特性

观察大鼠胚胎神经干细胞移植入成年大鼠纹状体后的存活、迁移和分化状况。自14天胎鼠脑室下区分离获得神经干细胞,利用无血清培养基培养扩增并进行鉴定。经4～5代的扩增后,以BrdU标记的神经干细胞通过脑立体定位注射移植入成年大鼠纹状体内,然后分别于移植后2周、4周、6周和8周时做脑冰冻切片,通过免疫组织化学和免疫荧光方法检测移植细胞的数量、定位和分化情况。8周后移植细胞的检出率约16%;移植细胞向周围宿主组织有广泛的迁移表现,尤以沿着白质束向头尾方向的迁移最为显著,最远向后侧达到内囊;纹状体中移植细胞主要分化为神经元和星形胶质细胞。星形胶质细胞数量最多,主要位于移植区与宿主组织临界部位,而神经元处于移植区中央。培养的大鼠胚胎神经干细胞可以作为移植替代治疗神经退行性疾病研究的供体细胞源,而移植中的迁移现象值得注意。     

人胚胎干细胞向神经上皮祖细胞的诱导分化

人胚胎干细胞具有自我更新和多向分化潜能,是研究早期胚胎发育和细胞替代治疗的重要细胞来源.采用一种与小鼠成纤维细胞共培养的方法进行人胚胎干细胞的神经诱导,可产生高纯度的神经上皮祖细胞,其神经上皮特异性基因的表达有一定的时空性;诱导生成的神经上皮祖细胞具有增殖潜能并可分化为神经元和星型胶质细胞,是潜在的神经干细胞.人胚胎干细胞来源的神经上皮祖细胞为研究神经发育和神经诱导提供了新材料,也为神经系统疾病的细胞替代治疗提供了新的细胞来源.     

利用成体干细胞治疗糖尿病

糖尿病是一类严重的代谢疾病, 正危害着世界上越来越多人口的健康。胰岛移植是一种治疗糖尿病的有效方法,却因供体缺乏和移植后免疫排斥问题制约了其广泛应用。干细胞为具有强增殖能力和多向分化潜能的细胞, 是利用细胞替代疗法治疗重大疾病的细胞来源之一, 其中成体干细胞因不存在致瘤性及伦理道德问题而被人们寄予厚望。成体胰腺干细胞在活体损伤及离体培养条件下均能产生胰岛素分泌细胞, 肝干细胞、骨髓干细胞和肠干细胞等在特定离体培养条件下或经过遗传改造后也均可产生胰岛素分泌细胞, 将这些干细胞来源的胰岛素分泌细胞移植到模型糖尿病小鼠中可以治疗糖尿病。因而, 成体干细胞可以为细胞替代疗法治疗糖尿病提供丰富的胰岛供体来源。     

大鼠脑神经干细胞系(RNSC-FMU 1)的建立和鉴定

采用无血清培养液分离和培养新生SD 大鼠脑的神经干细胞,以机械分散的方法传代,成功地建立了大鼠脑神经干细胞系(RSNC-FMU 1)。该细胞系可在体外长期传代,至今已在体外连续生长超过21个月(>100代),保持了神经干细胞的特性和正常的核型,经诱导可分化成为神经元、星形胶质细胞和少突胶质细胞,具有较旺盛的自新能力,倍增时间约为20h,并可冷冻保存,裸鼠体内移植证实其不具有成瘤性。该细胞系为神经干细胞研究提供了一个良好的工具。     

The neural stem cell niche

The neural stem cell niche defines a zone in which stem cells are retained after embryonic development for the production of new cells of the nervous system. This continual supply of new neurons and glia then provides the postnatal and adult brain with an added capacity for cellular plasticity, albeit one that is restricted to a few specific zones within the brain. Critical to the maintenance of the stem cell niche are microenvironmental cues and cell-cell interactions that act to balance stem cell quiescence with proliferation and to direct neurogenesis versus gliogenesis lineage decisions. Ultimately, based on the location of the niche, stem cells of the adult brain support regeneration in the dentate gyrus of the hippocampus and the olfactory bulb through neuron replacement. Here, we provide a summary of the current understanding of the organization and control mechanisms of the neural stem cell niche.     

Neural stem cells: mechanisms and modeling

In the adult brain, neural stem cells have been found in two major niches: the hippocampus and the olfactory bulb. Neurons derived from these stem cells contribute to learning, memory, and the autonomous repair of the brain under pathological conditions. Hence, the physiology of adult neural stem cells has become a significant component of research on synaptic plasticity and neuronal disorders. In addition, the recently developed induced pluripotent stem cell technique provides a powerful tool for researchers engaged in the pathological and pharmacological study of neuronal disorders. In this review, we briefly summarize the research progress in neural stem cells in the adult brain and in the neuropathological application of the induced pluripotent stem cell technique.     

Neural progenitor genes. Germinal zone expression and analysis of genetic overlap in stem cell populations

The identification of the genes regulating neural progenitor cell (NPC) functions is of great importance to developmental neuroscience and neural repair. Previously, we combined genetic subtraction and microarray analysis to identify genes enriched in neural progenitor cultures. Here, we apply a strategy to further stratify the neural progenitor genes. In situ hybridization demonstrates expression in the central nervous system germinal zones of 54 clones so identified, making them highly relevant for study in brain and neural progenitor development. Using microarray analysis we find 73 genes enriched in three neural stem cell (NSC)-containing populations generated under different conditions. We use the custom microarray to identify 38 "stemness" genes, with enriched expression in the three NSC conditions and present in both embryonic stem cells and hematopoietic stem cells. However, comparison of expression profiles from these stem cell populations indicates that while there is shared gene expression, the amount of genetic overlap is no more than what would be expected by chance, indicating that different stem cells have largely different gene expression patterns. Taken together, these studies identify many genes not previously associated with neural progenitor cell biology and also provide a rational scheme for stratification of microarray data for functional analysis.     

神经干细胞的分离、培养及应用前景

胚胎和成年哺乳动物脑内均存在神经干细胞,具有潜在的增值和分化能力。在一定条件下,神经干细胞可向多个方向分化,生成神经元和神经胶质细胞,这为利用神经干细胞进行中枢神经系统退行性病变和损伤的治疗打下基础。     

WJSC 6th Anniversary Special Issues（2）:Mesenchymal stem cells Brain mesenchymal stem cells:The other stem cells of the brain?

Multipotent mesenchymal stromal cells(MSC),have the potential to differentiate into cells of the mesenchymal lineage and have non-progenitor functions including immunomodulation.The demonstration that MSCs are perivascular cells found in almost all adult tissues raises fascinating perspectives on their role in tissue maintenance and repair.However,some controversies about the physiological role of the perivascular MSCs residing outside the bone marrow and on their therapeutic potential in regenerative medicine exist.In brain,perivascular MSCs like pericytes and adventitial cells,could constitute another stem cell population distinct to the neural stem cell pool.The demonstration of the neuronal potential of MSCs requires stringent criteria including morphological changes,the demonstration of neural biomarkers expression,electrophysiological recordings,and the absence of cell fusion.The recent finding that brain cancer stem cells can transdifferentiate into pericytes is another facet of the plasticity of these cells.It suggests that the perversion of the stem cell potential of pericytes might play an even unsuspected role in cancer formation and tumor progression.     

Neurogenesis in the Adult Mammalian Brain

The concept of the CNS cell composition stability has recently undergone significant changes. It was earlier believed that neurogenesis in the mammalian CNS took place only during embryonic and early postnatal development. New approaches make it possible to prove that neurogenesis takes part even in the adult brain. The present review summarizes the data about the neural stem cell. It has been demonstrated that new neurons are constantly formed in adult mammals, including man. In two brain zones, subventricular zone and dentate gyrus, neurogenesis appears to proceed throughout the entire life of mammals, including man. The newly arising neurons are essential for some important processes, such as memory and learning. Stem cells were found in the subependymal and/or ependymal layer. They express nestin and have a low mitotic activity. During embryogenesis, the stem cell divides asymmetrically: one daughter cell resides as the stem cell in the ependymal layer and another migrates to the subventricular zone. There it gives rise to a pool of dividing precursors, from which neural and glial cells differentiate and migrate to the sites of final localization. The epidermal and fibroblast growth factors act as mitogens for the neural stem cell. The neural stem cell gives rise to the cells of all germ layers in vitro and has a wide potential for differentiation in the adult organism. Hence, it can be used as a source of various cell types of the nervous tissue necessary for cellular transplantation therapy.     

干细胞巢研究进展

干细胞巢即干细胞周围的微环境构成,一般包括干细胞的相邻细胞、粘附分子及基质等,但不同的干细胞有不同的巢结构。干细胞巢通过不同信号途径调控着干细胞的行为,使干细胞的自我更新和分化处于平衡状态。根据近年来有关干细胞巢的研究,本文从果蝇生殖系干细胞巢、哺乳动物造血干细胞巢、肠干细胞巢、毛囊表皮干细胞巢和神经干细胞巢等五个系统分别综述了干细胞巢的构成及其对干细胞的调节作用,探讨了干细胞巢作用于干细胞的内在机制。     

Differentiation profile of brain tumor stem cells： a comparative study with neural stem cells

Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.     

TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation

In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells. In the absence of TRIM32, neuroblasts differentiate slower and show gene expression profiles that are characteristic of immature cells. Interestingly, TRIM32 deficiency induces more neural progenitor cell proliferation and less cell death. Both effects accumulate in an overproduction of adult-generated olfactory bulb neurons of TRIM32 knockout mice. These results highlight the function of the cell fate-determinant TRIM32 for a balanced activity of the adult neurogenesis process.