干细胞治疗神经系统疾病的研究进展

<正>干细胞是一类未分化的具有高度自我更新和多向分化潜能的细胞,包括胚胎干细胞和成体干细胞胚胎干细胞是全能性、无限增殖的干细胞,具有形成所有类型细胞的潜能,包括胚胎干细胞、胚胎生殖干细胞;成体干细胞包括神经干细胞、造血干细胞、骨髓间充质干细胞、表皮干细胞等,成体干细胞具有自我更新和分化为组织特异细胞的能力,即分化为相应组织和器官中细胞的专能细胞,它是存在于人体组织中的多潜能干细胞。按其分化潜能的大小,干     

骨髓干细胞移植在神经疾病中的应用前景

干细胞是指有多种分化潜能和自我更新能力的细胞 ,这种多潜能细胞存在于成年个体的许多组织和胚胎中。目前研究较为深入的干细胞主要有 :骨髓干细胞 ( MSC)、神经干细胞、胚胎干细胞。其中骨髓干细胞和神经干细胞已被认为具有令人鼓舞的潜能 ,多项实验研究结果表明 :骨髓干细胞和神经干细胞不仅可以修补各种组织器官 (如图 1 ) ,而且可治疗许多疾病。现对骨髓干细胞的有关研究概述如下。图 1　骨髓干细胞和神经干细胞作用于人体各种组织器官1　骨髓干细胞的基础研究1 .1　骨髓干细胞的特点和功能　　目前所知 ,骨髓干细胞至少包括两种干细…     

人类胚胎干细胞研究的伦理问题

干细胞即起源细胞 ,是指具有自我复制和多向分化潜能的原始细胞。按干细胞功能 ,将其分为全能干细胞、多能干细胞和专能干细胞。胚胎干细胞为全能干细胞 ,具有分化成几乎所有种类的细胞 ,甚至形成复杂的组织和器官的潜能。自从 1998年美国威斯康星大学Ｔｈｏｍｓｏｎ等人从人体     

中药对干细胞的作用研究进展

正干细胞是一类具有多向分化潜能和自我复制功能的早期未分化细胞,按其来源不同可分为胚胎干细胞和成体干细胞。在特定条件下,干细胞可以分化成功能不同的细胞,形成多种组织和器官。近年来,随着研究的逐渐深入,在越来越多的组织和器官中均发现了干细胞的存在~([1])。干细胞的多向分化潜能和自我复制功能,使其在组织结构和功能的维护更新及损     

骨髓干细胞移植在神经疾病中的应用前景

干细胞是指有多种分化潜能和自我更新能力的细胞,这种多潜能细胞存在于成年个体的许多组织和胚胎中.目前研究较为深入的干细胞主要有:骨髓干细胞(MSC)、神经干细胞、胚胎干细胞.     

成体干细胞移植研究现状

干细胞是指具有进一步分裂和分化潜能的细胞，其分化潜能因其来源不同而有很大差异。有的干细胞能分化为机体几乎所有的细胞类型，如胚胎干细胞，有的干细胞只能分化出一种细胞，如单能造血干细胞。在个体发育过程中，细胞的分化潜能逐渐变窄。根据其来源和发育阶段不同，可将干细胞分为4类：即胚胎癌细胞（embryonal stern cell，EC）、胚胎干细胞（embryonic stern cells，ES）、胚胎生殖细胞（embryonic germ cells，EG）和成年组织干细胞。从理论上讲，胚胎干细胞为全能干细胞，而成体组织干细胞则应为多能和／或单能干细胞。     

人体胚胎干细胞研究的伦理争论

干细胞是指在生命的生长和发育过程中起“主干”作用的原始细胞 ,它们具有自我更新、高度增殖和多向分化的潜能。尤其是人体胚胎干细胞(ＥＳｃｅｌｌｓ) ,它可以分化成人体全部 2 0 0多种细胞类型 ,进而构建人的心、肝、肾等各种组织和器官 ,最终发育成一个完整个体 ,因而是一种全能干细胞。干细胞和人体胚胎干细胞的研究 ,结合现代生物医学和工程技术 ,有可能使人类病变或衰老的组织或器官得以修复或替代 ,从而达到治疗癌症、自身免疫性疾病、神经退行性疾病 (如帕金森氏症、老年性痴呆 )等疑难性疾病的目的。因此 ,这种研究将成为 2 1世纪…     

干细胞治疗心肌损伤临床进展

干细胞研究是当今世界各国细胞生物工程领域的研究热点。随着对干细胞基础研究、应用研究的进一步深化 ,这项技术将会在相当大程度上引发医学领域的重大变革 ,它对医学发展有着十分重要意义 ,为人类战胜各种疾病 ,特别是肿瘤、自身免役性疾病、以及严重威胁人类健康的心血管疾病的治疗带来了全新的概念。1　干细胞概况　　干细胞是一类具有自我复制能力的多潜能细胞 ,在一定条件下 ,它可以分化成多种功能细胞。根据其发育阶段 ,干细胞可分为胚胎干细胞和成体干细胞 ,胚胎干细胞的分化和增殖构成动物发育的基础 ,即由单个受精卵发育成为具有…     

脂肪干细胞的研究及应用进展

干细胞在治疗各种疾病方面拥有巨大的潜能。在细胞治疗方面,脂肪干细胞是最有前景的种子细胞之一,其他的还包括胚胎干细胞和诱导的多能干细胞。胚胎干细胞和诱导的多能干细胞都具有多向分化潜能,因而起着举足轻重的作用。但是,胚胎干细胞和诱导的多能干细胞分别受限于伦理学问题及细胞表型的鉴定。脂肪干细胞则不受这些限制,不仅易于获取,而且方便扩增。在不同的诱导条件下,脂肪干细胞能分化为脂肪细胞、成骨细胞、软骨细胞、肌肉细胞、内皮细胞和神经细胞,这些分化潜能可应用于再生医学领域,如：皮肤重建,骨和软骨修复等。本篇综述着重讨论目前脂肪干细胞的分离、分化和治疗应用。     

人骨髓间充质干细胞成骨诱导的研究进展

<正>干细胞是一类具有自我复制能力的多潜能细胞,在一定条件下可分化为多种功能细胞,根据发育阶段不同分为胚胎干细胞和成体干细胞。骨髓间充质干细胞(Bone marrow-derived mesenchymal stem cells,BMSCs)是骨髓基质系统中的一类多能干细胞,具有向中胚层和神经外胚层来源组织细胞分化的能力。BMSCs获取简便,分离培养较容易,移植排斥反应较弱,植入反应较为理想。哺乳动物来源的BMSCs是具有多向分化潜能的成体干细胞,相关研究证实其有强烈的成骨潜     

建立植入前遗传学检测人胚胎来源的无动物源性干细胞系

【目的】在无动物源性的干细胞培养体系中建立植入前遗传学检测（PGT）胚胎来源的人胚胎干细胞系,为医学研究提供疾病模型。【方法】在我们的研究中,对无动物源性的人类包皮成纤维细胞饲养层（XF-HFF）与成分确定的培养基（CDM）构建的无动物源性培养体系进行了评估。在该培养体系中,利用染色体平衡易位患者PGT来源的废弃胚胎建立一个新的人胚干细胞（hESC）细胞系。【结果】新建立的人胚胎干细胞系在无动物源性培养系统中可长期培养传代（>45个代次）。核型分析显示,在传代45代次后,新建立的人胚胎干细胞仍保持一致的核型。XF-HFF/CDM中的hESC仍保持多能性。通过荧光免疫染色检测到SSEA-3、SSEA-4、SSEA-1、TRA-1-60、TRA-1-81等多能标志物的表达;RT-PCR分析显示,在XF-HFF/CDM培养体系上生长的hESC中存在干细胞标记。小鼠体内实验也证实了hESC在体内维持其多能性。【结论】本研究建立了PGT来源的人胚胎干细胞系,为进一步建立携带遗传疾病基因的hESC系并为临床研究和治疗提供疾病模型打下了基础。     

人胚胎多能干细胞研究中的几个问题

目前在人胚胎多能干细胞的研究中存在材料来源不足、培养体系复杂和自发性分化的问题.这3个基本问题限制了人胚胎多能干细胞的基础和临床应用研究.要建立新的胚胎多能干细胞系应利用细胞核移植和细胞质重新编程功能建立新的途径,并探讨其中的机制和可能的关键因子;干细胞培养时主要进行简化培养体系和抑制细胞分化的研究;对干细胞分化进行临床应用研究时,主要将多种方法联合应用来诱导和筛选目的细胞并对其形态和功能进行评价.     

Derivation and characterization of Chinese human embryonic stem cell line with high potential to differentiate into pancreatic and hepatic cells

Background  Human embryonic stem cells have prospective uses in regenerative medicine and drug screening. Every human embryonic stem cell line has its own genetic background, which determines its specific ability for differentiation as well as susceptibility to drugs. It is necessary to compile many human embryonic stem cell lines with various backgrounds for future clinical use, especially in China due to its large population. This study contributes to isolating new Chinese human embryonic stem cell lines with clarified directly differentiation ability.

Methods  Donated embryos that exceeded clinical use in our in vitro fertilization-embryo transfer (IVF-ET) center were collected to establish human embryonic stem cells lines with informed consent. The classic growth factors of basic fibroblast growth factor (bFGF) and recombinant human leukaemia inhibitory factor (hLIF) for culturing embryonic stem cells were used to capture the stem cells from the plated embryos. Mechanical and enzymetic methods were used to propogate the newly established human embryonic stem cells line. The new cell line was checked for pluripotent characteristics with detecting the expression of stemness genes and observing spontaneous differentiation both in vitro and in vivo. Finally similar step-wise protocols from definitive endoderm to target specific cells were used to check the cell line’s ability to directly differentiate into pancreatic and hepatic cells.

Results  We generated a new Chinese human embryonic stem cells line, CH1. This cell line showed the same characteristics as other reported Chinese human embryonic stem cells lines: normal morphology, karyotype and pluripotency in vitro and in vivo. The CH1 cells could be directly differentiated towards pancreatic and hepatic cells with equal efficiency compared to the H1 cell line.

Conclusions  This newly established Chinese cell line, CH1, which is pluripotent and has high potential to differentiate into pancreatic and hepatic cells, will provide a useful tool for embryo development research, along with clinical treatments for diabetes and some hepatic diseases.

     

人成纤维细胞对人胚胎干细胞生长的支持作用

目的观察人成纤维细胞对人胚胎干细胞（hESC）生长的支持作用，建立完全非动物源性培养系统。方法采用人包皮成纤维细胞为饲养层，以血清替代品取代动物血清，支持人胚胎干细胞生长，观察其增殖和分化情况。结果包皮成纤维细胞能很好地支持人胚胎干细胞生长增殖，并保持87％左右未分化表型：碱性磷酸酶（AKP）染色强阳性，阶段特异性胚胎抗原3（SSEA-3），肿瘤排斥抗原160（TRA-1-60）表达强阳性，可见转录因子OCT-4mRNA表达。核型正常，体外能形成拟胚体。结论人成纤维细胞完全可以支持人胚胎干细胞增殖，可望为胚胎干细胞定向诱导分化应用于临床打下基础。     

Stem cells, embryos, and the environment: a context for both science and ethics

Debate on the potential and uses of human stem cells tends to be conducted by two constituencies-ethicists and scientists. On many occasions there is little communication between the two, with the result that ethical debate is not informed as well as it might be by scientific insights. The aim of this paper is to highlight those scientific insights that may be of relevance for ethical debate. Environmental factors play a significant role in identifying stem cells and their various subtypes. Research related to the role of the microenvironment has led to emphasis upon "plasticity", which denotes the ability of one type of stem cell to undergo a transition to cells from other lineages. This could increase the value given to adult stem cells, in comparison with embryonic stem cell research. Any such conclusion should be treated with caution, however, since optimism of this order is not borne out by current research. The role of the environment is also important in distinguishing between the terms totipotency and pluripotency. We argue that blastocysts (early embryos) and embryonic stem cells are only totipotent if they can develop within an appropriate environment. In the absence of this, they are merely pluripotent. Hence, blastocysts in the laboratory are potentially totipotent, in contrast to their counterparts within the human body which are actually totipotent. This may have implications for ethical debate, suggesting as it does that arguments based on potential for life may be of limited relevance.     

Establishment of human embryonic stem cell line from gamete donors

Background Human embryonic stem (HES) cell derived from human blastocyst can be propagated indefinitely in the primitive undifferentiated state while remaining pluripotent. It has exciting potential in human developmental biology, drug discovery, and transplantation medicine. But there are insufficient HES cell lines for further study. Methods Three oocyte donors were studied, and 3 in vitro fertilization (IVF) cycles were carried out to get blastocysts for the establishment of HES cell line. Isolated from blastocysts immunosurgically, inner cell mass (ICM) was cultured and propagated on mouse embryonic fibroblasts (MEFs). Once established, morphology, cell surface markers, karyotype and differentiating ability of the cell line were thoroughly analyzed. Results Four ICMs from 7 blastocysts were cultured on MEFs. After culture, one cell line ( criES-1 ) was established and met the criteria for defining human pluripotent stem cells including a series of markers used to identify pluripotent stem cells, morphological similarity to primate embryonic stem cells and HES reported else where. Normal and stable karyotype maintained over 60 passages, and demonstrated ability to differentiate into a wide variety of cell types. Conclusions HES cell lines can be established from gamete donors at a relatively highly efficient rate. The establishment will exert a widesoread impact on biomedical research.     

胚胎干细胞诱导分化机制及方法

胚胎干细胞是来源于附植前胚胎的内细胞团或附植后胎儿的原始生殖细胞具有发育全能性的细胞。近年来在胚胎干细胞分化机制研究和定向诱导分化方面都有长足进展，但其分化机制和定向分化的方法一直是人们需要解决的难点问题，本文主要就胚胎干细胞的定向分化机制、方法及目前存在的问题等方面进行概括性论述。     

人类3D大脑类器官研究进展

人类3D大脑类器官为研究人脑发育和神经系统疾病提供了新的模型。体外培育的人类3D大脑类器官主要是由人多能干细胞（human pluripotent stem cell,hPSC）,包括人胚胎干细胞（embryonic stem cell,ESC）和诱导多能干细胞（induced pluripotent stem cell,iPSC）分化而来。iPSC重编程技术与3D大脑类器官技术相结合,可以获得来自患者的iPSC并分化成包括神经元及大脑类器官在内的几乎任何人体细胞或组织,是动物实验向临床试验转化的桥梁。本文回顾了从多能干细胞技术到3D大脑类器官诞生并发展的历程,介绍了以3D大脑类器官为工具构建脑发育和神经系统疾病的研究模型,讨论了大脑类器官在其他方面的应用和相关技术的研究进展,并分析了3D大脑类器官的局限性及其未来可能的发展方向。     

Neural stem cells: Brain building blocks and beyond

Abstract

Neural stem cells are the origins of neurons and glia and generate all the differentiated neural cells of the mammalian central nervous system via the formation of intermediate precursors. Although less frequent, neural stem cells persevere in the postnatal brain where they generate neurons and glia. Adult neurogenesis occurs throughout life in a few limited brain regions. Regulation of neural stem cell number during central nervous system development and in adult life is associated with rigorous control. Failure in this regulation may lead to e.g. brain malformation, impaired learning and memory, or tumor development. Signaling pathways that are perturbed in glioma are the same that are important for neural stem cell self-renewal, differentiation, survival, and migration. The heterogeneity of human gliomas has impeded efficient treatment, but detailed molecular characterization together with novel stem cell-like glioma cell models that reflect the original tumor gives opportunities for research into new therapies. The observation that neural stem cells can be isolated and expanded in vitro has opened new avenues for medical research, with the hope that they could be used to compensate the loss of cells that features in several severe neurological diseases. Multipotent neural stem cells can be isolated from the embryonic and adult brain and maintained in culture in a defined medium. In addition, neural stem cells can be derived from embryonic stem cells and induced pluripotent stem cells by in vitro differentiation, thus adding to available models to study stem cells in health and disease.     

诱导性多能干细胞相关基因Oct4、Sox2、Nanog的研究进展

诱导性多能干细胞(iPSCs)是将转录因子转入已分化的体细胞中,使其重编程而得到的类似胚胎干细胞(ESCs)的一种细胞类型。iPSCs细胞在形态、基因和蛋白表达、表观遗传修饰状态、细胞倍增能力、类胚体和畸形瘤生成能力、分化能力等方面都与ESCs相似。iPSCs细胞假说一经提出,使得相关基因(如Oct4、Sox2、Nanog等)再次成为基础研究和基因治疗的重要选择。