诱导多功能干细胞(iPSC)技术的研究进展

诱导多功能干细胞(iPSC)是采用基因重排的方法,使已分化的成体细胞重新获得多向分化潜能的细胞.由于它具有多种组织分化的特性,不存在伦理方面的争议,成为再生医学领域的研究热点.小鼠、人的多种分化的成体细胞已被成功诱导为具有多向分化潜能的多功能干细胞.诱导分化技术不断得到验证与改进,正在逐步得到推广,为iPS细胞向临床应用打下了坚实的基础.     

植物诱导抗病性及应用前景

就植物诱导抗病性的概念、防御反应及功能事件和信号传导应用前景作了简单的总结。     

再编程诱导多功能干细胞的研究现状和应用前景

干细胞（stem ceils．SC）是一类具有自我复制能力（self-renewing）的多潜能细胞,在一定条件下．它可以分化成多种功能细胞。自从20世纪末美国Science（《科学》）杂志连续两年将干细胞生物学和干细胞生物工程评为世界十大科学成就之首以来．干细胞领域就持续成为国内外医学和生物学研究的热点。2007年11月20日,《细胞》和《科学》杂志分别发表了日本和美国研究人员各自独立完成的一项研究．     

诱导多能干细胞(iPS)的诱导培养与鉴定

通过外源转录调控因子的诱导,使成体细胞重编程为胚胎干细胞(ES细胞)样的多能细胞,这种细胞称为诱导多能干细胞(iPS细胞),这一方法被称为iPS技术。目前,iPS技术已先后在小鼠、人、猕猴、大鼠和猪中成功应用,建立了相应的iPS细胞系,并获得了iPS细胞嵌合小鼠和四倍体克隆小鼠。尽管iPS与ES细胞在形态和生长特性上有许多相同之处,但iPS细胞的建立需要较独特的诱导培养体系和鉴定方法。以下结合近年来iPS技术的发展和本实验室的相关研究,对iPS细胞的建立和培养体系的优化进行了深入探讨。     

诱导多功能干细胞治疗阿尔茨海默病的研究进展

阿尔茨海默病(Alzheimer’s disease,AD)是一种多因素相关的复杂性疾病,临床主要表现为记忆力逐渐丧失和认知功能障碍.目前尚无有效的治疗方法.由AD病人来源的诱导多功能干细胞(induced pluripotent stem cells,iPSCs)分化成的神经元具有AD的相关病理表现,是AD发病机制研究和潜在药物筛选的模型之一.由于iPSCs的分化潜能,iPSCs又能分化为不同类型的神经细胞改善AD的症状.iPSCs相关研究成为目前AD研究的热点之一.本文主要综述iPSCs在AD病理机制研究和AD治疗中的作用.     

浅谈干细胞的研究现状与应用前景

1999年 ,《Science》将人类胚胎干细胞研究成果评为当年世界十大科技进展之首 ,2 0 0 0年 ,《Time》周刊将其列为 2 0世纪末世界十大科技成就之首 ,并认为胚胎干细胞和人类基因组将同时成为新世纪最具发展和应用前景的领域。干细胞的研究为什么会引起人们的如此关注 ?本文将对此作一简要介绍。1　干细胞的概念干细胞是在生物个体的生长和发育中起“主干”作用的原始细胞 ,具有自我更新、高度增殖和多向分化潜能的细胞群体 ,即这些细胞可以通过细胞分裂维持自身细胞群的大小 ,同时又可以进一步分化成为各种不同的组织细胞 ,从而构成机体各种…     

人诱导多能干细胞分化为心肌细胞关键基因的生物信息学分析

利用生物信息学分析的方法筛选人诱导多能干细胞(induced pluripotent stem cells, i PSCs)向心肌细胞分化的关键基因。收集GEO (Gene Expression Omnibus)数据库中关于人i PSCs向心肌细胞分化的高通量测序数据,包含i PSCs向心肌细胞分化的4个阶段的样本数据,分别是未分化的i PSCs (D0)、中胚层细胞(D2)、早期心肌细胞(D7)和心肌细胞(D14)。应用R包分析D0、D2、D7和D14样品之间的差异表达基因,并对差异表达基因进行功能和信号通路分析;构建差异表达基因的蛋白质-蛋白质互作(protein-protein interaction, PPI)网络;应用R包加权基因共表达网络分析(weighted gene co-expression network analysis, WGCNA)对共表达的基因进行聚类,并将其划分为不同的基因模块;使用Cytoscape软件对重要基因模块的互作网络进行可视化和富集分析。结果显示, D0、D2、D7和D14样品之间的差异表达基因总共达917个,基于PPI网络筛选到的前10个基因...     

干细胞研究概述及其应用前景

简要介绍干细胞的涵义、分类及其生物性质,并着重指出其可能的应用前景。     

成体干细胞的生物学特点及应用前景

成体干细胞存在于人和哺乳动物组织中,具有自我更新和一定的分化潜能,现已从骨髓,软骨,血液,神经,肌肉,脂肪,皮肤,角膜缘,肝脏,胰腺等许多组织中获得成体干细胞,发现部分组织成体干细胞具有多向分化潜能,成体干细胞的研究在再生医学中有十分广阔的应用前景。     

神经干细胞--治疗脑神经性疾病的希望(2)

(续 2 0 0 2年第 1期第 7页 )5　成体神经干细胞的起源大量事实表明 ,在鼠脑、灵长类和人脑中均存在新生的神经细胞。这些细胞究竟起源于哪些脑区 ,它们产生后是怎样迁移的并形成什么类型的神经元 ?显然 ,这都是具有挑战性的课题。现在可以肯定的是 ,成体人脑中有 3个脑区具有神经干细胞。其中最重要的脑区为室管膜下层 (subven-tricular zone,SVZ) ,其他的两个脑区为海马的齿状回和嗅回。SVZ紧邻大脑的侧脑室壁 ,这是一个重要的神经发生区 ,它的神经发生能力可保持终生。海马是与学习和记忆有关的重要脑区。哺乳动物的大部分脑区 ,其细…     

Prospects and challenges of induced pluripotent stem cells as a source of hematopoietic stem cells

Many life-threatening hematological diseases are now treated by bone marrow transplantations, i.e., infusion of hematopoietic stem cells (HSCs). HSC transplantations are a valid option for the treatment of a variety of metabolic disorders, and even for solid tumors and some refractory severe autoimmune diseases. Unfortunately, the frequency and outcome of HSC transplantations are limited by a shortage of suitable donors. Induced pluripotent stem cells (iPSCs)-somatic cells that have acquired pluripotent stem cell characteristics by the ectopic expression of pluripotency-inducing factors-have been proposed as an alternative source of HSCs. Possible applications include cells of autologous, of autologous and genetically modified, or of allogeneic origin. Here, we provide a perspective on the distinct opportunities of iPSCs and discuss the challenges that lie ahead.     

Mouse induced pluripotent stem cells

The recent discovery that it is possible to directly reprogramme somatic cells to an embryonic stem (ES) cell-like pluripotent state, by retroviral transduction of just four genes (Oct3/4, Sox2, c-Myc and Klf4), represents a major breakthrough in stem cell research. The reprogrammed cells, known as induced pluripotent stem (iPS) cells, possess many of the properties of ES cells, and represent one of the most promising sources of patient-specific cells for use in regenerative medicine. While the ultimate goal is the use of iPS cells in the treatment of human disease, much of the research to date has been carried out with murine cells, and improved mouse iPS cells have been shown to contribute to live chimeric mice that are germ-line competent. Very recently, it has been reported that iPS cells can be generated by three factors without c-Myc, and these cells give rise to chimeric mice with a reduced risk of tumour development.     

Disease-specific induced pluripotent stem cells

Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumor cell lines or transformed derivatives of native tissues. Here we describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; these diseases include adenosine deaminase deficiency-related severe combined immunodeficiency (ADA-SCID), Shwachman-Bodian-Diamond syndrome (SBDS), Gaucher disease (GD) type III, Duchenne (DMD) and Becker muscular dystrophy (BMD), Parkinson disease (PD), Huntington disease (HD), juvenile-onset, type 1 diabetes mellitus (JDM), Down syndrome (DS)/trisomy 21, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.     

Application of induced pluripotent stem cells to hematologic disease

Induced pluripotent stem cells (iPSC) were first generated from somatic cells via the transduction of four ‘Yamanaka’ factors, Oct4, Sox2, Klf4 and c-Myc. Because iPSC are similar to embryonic stem cells (ESC) and can be differentiated into any cell type of choice, iPSC have the potential to become a platform for personalized medicine by allowing a patient's own cells to become a source of therapeutic tissue. This review describes the main challenges in iPSC technology by focusing on its application to hematologic diseases. The explosive interest in improving iPSC technology has generated numerous genetic and chemical methods for iPSC derivation, but these methods must be evaluated comparatively for their safety and efficacy because there are risks of genetic abnormalities and oncogenesis. Competent iPSC will need to be selected carefully based on physical, genetic and functional criteria, and differentiated efficiently into hematopoietic stem cells via modulation of several signaling pathways before they prove valuable in the clinic.     

Methods to produce induced pluripotent stem cell-derived mesenchymal stem cells: Mesenchymal stem cells from induced pluripotent stem cells

Mesenchymal stem cells (MSCs) have received significant attention in recent years due to their large potential for cell therapy. Indeed, they secrete a wide variety of immunomodulatory factors of interest for the treatment of immune-related disorders and inflammatory diseases. MSCs can be extracted from multiple tissues of the human body. However, several factors may restrict their use for clinical applications: the requirement of invasive procedures for their isolation, their limited numbers, and their heterogeneity according to the tissue of origin or donor. In addition, MSCs often present early signs of replicative senescence limiting their expansion in vitro, and their therapeutic capacity in vivo. Due to the clinical potential of MSCs, a considerable number of methods to differentiate induced pluripotent stem cells (iPSCs) into MSCs have emerged. iPSCs represent a new reliable, unlimited source to generate MSCs (MSCs derived from iPSC, iMSCs) from homogeneous and well-characterized cell lines, which would relieve many of the above mentioned technical and biological limitations. Additionally, the use of iPSCs prevents some of the ethical concerns surrounding the use of human embryonic stem cells. In this review, we analyze the main current protocols used to differentiate human iPSCs into MSCs, which we classify into five different categories: MSC Switch, Embryoid Body Formation, Specific Differentiation, Pathway Inhibitor, and Platelet Lysate. We also evaluate common and method-specific culture components and provide a list of positive and negative markers for MSC characterization. Further guidance on material requirements to produce iMSCs with these methods and on the phenotypic features of the iMSCs obtained is added. The information may help researchers identify protocol options to design and/or refine standardized procedures for large-scale production of iMSCs fitting clinical demands.     

诱导多能干细胞在心血管疾病研究和治疗中的应用

诱导多能干细胞（induced pluripotent stem cells,iPS细胞）不仅具有与胚胎干细胞（embryonic stem cell,ESC）相似的各项特性,相对于ESC,iPS细胞,尤其患者特异性iPS细胞还具有来源方便、不存在免疫排斥和伦理问题以及可以保留特定个体基因型等优点,为再生医学提供了可能的细胞来源。该文主要从心血管药物的筛选、疾病模型的建立、iPS细胞应用于心脏移植研究等方面入手,探讨了iPS细胞在心血管疾病研究和治疗中的现状和未来。     

The business of exploiting induced pluripotent stem cells

Induced pluripotent stem cells (iPS cells) can be exploited for both research and clinical applications. The first part of this review seeks to provide an understanding of the financial drivers and key elements of a successful business strategy that underpin a company focused on developing iPS-related products and services targeted at the research market. The latter part of the review highlights some of the reasons as to why the reprogramming of somatic cells is currently being used to develop cell-based models to screen for small molecules with drug-like properties rather than to develop cell-based regenerative medicines per se. The latter may be used to repair or replace a patient's damaged cells and thereby have the potential to 'cure' a disease and, in doing so, prevent or delay the onset of associated medical conditions. However, the cost of an expensive regenerative medicine and time to accrue any benefit linked to a decrease in co-morbidity expenditure may not outweigh the benefit for a healthcare community that has finite resources. The implications of this are discussed together with evidence that the UK National Institute for Health and Clinical Excellence (NICE) and the National Health Service (NHS) have established a precedent for a cost-sharing strategy with the pharmaceutical industry.     

The genomic stability of induced pluripotent stem cells

With their capability to undergo unlimited self-renewal and to differentiate into all cell types in the body, induced pluripotent stem cells (iPSCs), reprogrammed from somatic cells of human patients with defined factors, hold promise for regenerative medicine because they can provide a renewable source of autologous cells for cell therapy without the concern for immune rejection. In addition, iPSCs provide a unique opportunity to model human diseases with complex genetic traits, and a panel of human diseases have been successfully modeled in vitro by patient-specific iPSCs. Despite these progresses, recent studies have raised the concern for genetic and epigenetic abnormalities of iPSCs that could contribute to the immunogenicity of some cells differentiated from iPSCs. The oncogenic potential of iPSCs is further underscored by the findings that the critical tumor suppressor p53, known as the guardian of the genome, suppresses induced pluripotency. Therefore, the clinic application of iPSCs will require the optimization of the reprogramming technology to minimize the genetic and epigenetic abnormalities associated with induced pluripotency.