胚胎干细胞

胚胎干细胞具有自我复制并分化为人体各种功能细胞的潜能。胚胎干细胞具有的独特生物学特性使其被广泛应用于生物学研究的各个领域,特别是发育学。同时,它潜在的医学应用也成为世界范围内的研究热点。但是,由于人胚胎干细胞的来源为植入前的早期胚胎,人胚胎干细胞自诞生之日起便倍受争议。本文将从胚胎干细胞的来源、特性、鉴定标准、增殖机理、应用前景以及研究本身涉及的伦理学争论给予概述。     

Embryonic stem cells

Embryonic stem cells have huge potential in the field of tissue engineering and regenerative medicine as they hold the capacity to produce every type of cell and tissue in the body. In theory, the treatment of human disease could be revolutionized by the ability to generate any cell, tissue, or even organ, 'on demand' in the laboratory. This work reviews the history of murine and human ES cell lines, including practical and ethical aspects of ES cell isolation from pre-implantation embryos, maintenance of undifferentiated ES cell lines in the cell culture environment, and differentiation of ES cells in vitro and in vivo into mature somatic cell types. Finally, we discuss advances towards the clinical application of ES cell technology, and some of the obstacles which must be overcome before large scale clinical trials can be considered.     

Embryonic potential and stem cells

This paper examines three arguments that use the concept of potential to identify embryos that are morally suitable for embryonic stem cell research (ESCR). According to the first argument, due to Ronald Green, the fact that they are scheduled for disposal makes embryos left over from IVF treatments morally appropriate for research. Paul McHugh argues that embryos created by somatic cell nuclear transfer differ from those that result directly from the meeting of sperm and egg in having potential especially conducive to the therapeutic use of their stem cells. I reject both of these arguments. According to the way of making distinctions in embryonic potential that I defend, it is the absence of a functional relationship with a womb that marks embryos morally suitable for ESCR.     

培养于生物降解支架膜内的胚胎干细胞可修复小鼠的梗塞心肌

我们以往的研究表明,直接在心肌梗塞（myocardial infarction,MI）动物的心脏缺血区注射胚胎干细胞（embryonic stemceils,ESCs）可以提高其心肌功能,干细胞组织工程学可以使组织再生、修复。本研究旨在观察将ESCs接种到生物降解膜内并移植到梗塞部位的效果。通过结扎小鼠左冠状动脉制作MI模型,将培养3d的带有小鼠ESCs的聚羟基乙酸膜（polyglycolicacid,PGA）移植到心肌缺血及边缘区表面。实验小鼠分成4组：假手术组、MI组、MI＋PGA组、MI＋ESC组,移植操作8周后检测血流动力学和心肌功能。MI组的血压和左心室功能显著降低。与MI组和MI＋PGA组相比,MI＋ESC组的血压和心室功能显著改善,存活率也显著增高,在梗塞区检测到GFP阳性组织,表明ESCs存活,并可能有心肌再生。以上结果表明,移植生物降解膜内的ESCs可修复小鼠梗塞区心肌细胞并提高心脏功能。将ESCs和生物降解材料联合运用可能为修复受损心脏提供一个新的治疗方法。     

鱼类的胚胎干细胞

胚胎干细胞(ES)是未分化的细胞培养物，来自动物的早期胚胎。它们能成为稳定的细胞系和长期冻存。在适当的条件下，ES细胞能分化成各种细胞类型，包括生殖细胞。这样，ES细胞就提供了一个有效的纽带，将动物基因组的体外和体内遗传操作连系起来。ES细胞的魅力就由其在产生和分析基因敲除老鼠中显现出来。目前，ES细胞技术仅见之老鼠，因其它脊椎动物的ES细胞的培养和建系难获成功。在鱼类，人们已做了大量的尝试。我们以青鳉(Oryzias latipes)作为建立鱼类ES细胞技术的模式，通过建立并应用无滋养层细胞的培养条件，获得了来自中期囊胚的ES细胞系。青鳉的ES细胞和老鼠的ES细胞有很多共同特征，如二倍体核型、分化潜力和形成嵌合体。因此，在鱼类建立和应用ES细胞技术是可能的。青鳉ES细胞的培养条件已成功地应用到其它鱼类如斑马鱼甚至海水鱼。本文旨在以青鳉为模式，综述获得和应用模式鱼和经济鱼ES细胞的主要进展和前景。     

Embryonic origins of adult pluripotent stem cells

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Embryonic cortical neural stem cells migrate ventrally and persist as postnatal striatal stem cells

Embryonic cortical neural stem cells apparently have a transient existence, as they do not persist in the adult cortex. We sought to determine the fate of embryonic cortical stem cells by following Emx1(IREScre); LacZ/EGFP double-transgenic murine cells from midgestation into adulthood. Lineage tracing in combination with direct cell labeling and time-lapse video microscopy demonstrated that Emx1-lineage embryonic cortical stem cells migrate ventrally into the striatal germinal zone (GZ) perinatally and intermingle with striatal stem cells. Upon integration into the striatal GZ, cortical stem cells down-regulate Emx1 and up-regulate Dlx2, which is a homeobox gene characteristic of the developing striatum and striatal neural stem cells. This demonstrates the existence of a novel dorsal-to-ventral migration of neural stem cells in the perinatal forebrain.     

Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells

Pluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref. 1). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive epigenetic marks. In contrast, EpiSCs have activated the epigenetic machinery that supports differentiation towards the embryonic cell types. The transition from naive to primed pluripotency therefore represents a pivotal event in cellular differentiation. But the signals that control this fundamental differentiation step remain unclear. We show here that paracrine and autocrine Wnt signals are essential self-renewal factors for ESCs, and are required to inhibit their differentiation into EpiSCs. Moreover, we find that Wnt proteins in combination with the cytokine LIF are sufficient to support ESC self-renewal in the absence of any undefined factors, and support the derivation of new ESC lines, including ones from non-permissive mouse strains. Our results not only demonstrate that Wnt signals regulate the naive-to-primed pluripotency transition, but also identify Wnt as an essential and limiting ESC self-renewal factor.     

Embryonic stem cells: testing the germ-cell theory

The exact cellular origin of embryonic stem cells remains elusive. Now a new study provides compelling evidence that embryonic stem cells, established under conventional culture conditions, originate from a transient germ-cell state.     

Current focus of stem cell application in retinal repair

The relevance of retinal diseases, both in society’s economy and in the quality of people’s life who suffer with them, has made stem cell therapy an interesting topic forresearch. Embryonic stem cells(ESCs), induced pluripotent stem cells(i PSCs) and adipose derived mesenchymal stem cells(ADMSCs) are the focus in current endeavors as a source of different retinal cells, such as photoreceptors and retinal pigment epithelial cells. The aim is to apply them for cell replacement as an option for treating retinal diseases which so far are untreatable in their advanced stage. ESCs, despite the great potential for differentiation, have the dangerous risk of teratoma formation as well as ethical issues, which must be resolved before starting a clinical trial. i PSCs, like ESCs, are able to differentiate in to several types of retinal cells. However, the process to get them for personalized cell therapy has a high cost in terms of time and money. Researchers are working to resolve this since i PSCs seem to be a realistic option for treating retinal diseases. ADMSCs have the advantage that the procedures to obtain them are easier. Despite advancements in stem cell application, there are still several challenges that need to be overcome before transferring the research results to clinical application. This paper reviews recent research achievements of the applications of these three types of stem cells as well as clinical trials currently based on them.