诱导性多能干细胞的研究概况

诱导性多能干细胞（induced pluripotent stem cells,iPS细胞）是通过在分化的体细胞中表达特定的几个转录因子,以诱导体细胞的重编程而获得的可不断自我更新且具有多向分化潜能的细胞。诱导性多能干细胞具有获取方便、能向各类细胞分化及无限增殖等特性。本文就诱导性多能干细胞的产生、制备技术的优化及应用前景等方面作一概述。     

干细胞与心肌再生

由于成年心肌细胞通常不能再生,严重的心肌损伤会导致心肌不可逆的重构坏死, 从而发生心功能失调. 干细胞再生治疗为心肌再生提供了很好的策略. 为了寻找合适的干细胞类型, 促进心肌再生, 有效改善心功能, 需要更好地了解心肌修复和再生的分子基础. 已有研究发现多种干细胞可促进心肌再生. 描述了骨髓干细胞的促血管新生及心肌分化的能力在心梗治疗中的作用, 还讨论了心脏侧群干细胞以及诱导型多能干细胞在心肌再生中的作用和分子机制. 所阐述的最新数据有利于拓展干细胞治疗的有效潜能及临床影响.     

诱导性多能干细胞的发展及前景展望

近年来,通过转入特定基因诱导体细胞重编程成为多能干细胞（iPS细胞）的研究成果引起了生命科学领域新的轰动。将完全分化的细胞重编程。不经过胚胎逆转为多能干细胞状态,这种方法相对容易操作,比较稳定,在生物学基础研究和临床应用方面都具有潜在的实用价值。与胚胎干细胞（ESC）相似,iPS细胞对于生物制药品种的更新和产生等十分有益。iPS细胞的产生对解决长期以来干细胞研究领域的伦理问题和免疫排斥问题具有十分重要的意义。然而,目前iPS技术仍然存在致癌性、效率低、病毒载体欠安全以及移植后存活率低等一系列问题。本文从iPS细胞的发展、获得、存在的问题以及发展前景4个方面进行了介绍。     

诱导肿瘤细胞HeLa为多能性干细胞的研究

将携带4种转录因子的逆转录病毒共同感染HeLa细胞,感染后的细胞铺到滋养层细胞MEF上培养,细胞长出类似胚胎干细胞的克隆团,这种克隆团可以扩增,并进一步诱导分化为神经元,同时免疫荧光检测细胞分化不同天数后Pax6,Sox1和βⅢ-tubulin的表达.结果表明,肿瘤细胞HeLa在Oct4、Sox2、c-Myc、Klf4等4种转录因子的作用下成功重编程为多能干细胞,同时可进一步分化为神经元.     

诱导性多能干细胞研究及应用

诱导性多能干细胞（iPS细胞）是通过向体细胞中导入Oct4,Sox2,c-myc和KU4等基因,使体细胞重编程获得具有胚胎干细胞样特性的多能干细胞．iPS细胞的产生可谓干细胞领域的新里程碑．近两年,iPS细胞的研究突飞猛进,文中结合最新的研究结果,综述了iPS细胞的研究现状、进展,如新的iPS细胞诱导方法的建立、诱导iPS细胞产生效率的提高、iPS细胞的定向诱导分化及其在疾病模型治疗中的作用等．针对iPS细胞研究领域存在的问题,包括如何提高iPS细胞生成的效率、解决其临床应用的安全性、iPS细胞重编程的机制等进行了讨论,为今后进一步开展iPS细胞的研究提供了帮助．     

诱导性多能干细胞研究及应用

诱导性多能干细胞(iPS细胞)是通过向体细胞中导入Oct4,Sox2,c-myc 和 Klf4 等基因,使体细胞重编程获得具有胚胎干细胞样特性的多能干细胞.iPS细胞的产生可谓干细胞领域的新里程碑.近两年,iPS细胞的研究突飞猛进,文中结合最新的研究结果,综述了iPS细胞的研究现状、进展,如新的iPS细胞诱导方法的建立、诱导iPS细胞产生效率的提高、iPS细胞的定向诱导分化及其在疾病模型治疗中的作用等.针对iPS细胞研究领域存在的问题,包括如何提高iPS细胞生成的效率、解决其临床应用的安全性、iPS细胞重编程的机制等进行了讨论,为今后进一步开展iPS细胞的研究提供了帮助.     

诱导多能干细胞与帕金森症

两篇新文章让我们对帕金森症的基本认识更进了一步。在论文#7中,麻省坎布里奇白头生物医药研究所的Rudolf Jaenisch团队描绘了一个方案,这一方案可以将帕金森病人的皮肤细胞重编程成多能干细胞,而且不会有以前那些重编程方法的缺点。     

揭示体细胞“变身”多能干细胞诱导机制——中科院广州生物医药与健康研究院获省科学技术奖一等奖

<正>2006年以来,诱导多能干细胞成为干细胞领域的研究热点。诱导多能干细胞的发现有望克服干细胞治疗面临的伦理学争议和免疫排斥问题,被认为是再生医学领域最为理想的供体细胞来源。利用诱导多能性干细胞进行细胞药物研发、药物筛选将会为多种疾病的治疗提供有效的治疗方案。然而,在体细胞变身多能干细胞研究过程中,还有大量     

德国科学家重组人类羊水细胞获得诱导多能干细胞

羊水细胞比其它普通类型的细胞有很多优点,首先,正常情况下羊水细胞在孕妇临产前就能够被提取,并且这些羊水细胞可以被重组建立大量的多能干细胞（iPS细胞）,医生可以通过对这些被重组的羊水细胞进行检查来判断孕妇是否患有疾病;其次,羊水混合物中包含有各种类型胎儿的体内细胞,     

非编码RNA调控心脏重构与再生

近年来, 越来越多的证据表明, 大量的非编码RNA(non-coding RNAs, ncRNAs)在基因的表达调控、细胞和机体的生理功能维持与病理环境调节方面都有重要作用, 其中主要包括微小RNA(microRNAs, miRNAs) 和长链非编码RNA(long non-coding RNAs, lncRNAs).心脏重构与再生是心血管疾病领域的关键问题, 其调控过程非常复杂, 包括表观遗传、转录、转录后及翻译水平的调控. 大量研究发现在转录后水平, miRNAs 通过负性调节靶标的表达调控心脏发育、疾病及再生进程. 近期研究揭示, lncRNAs 在心脏发育和疾病中具有潜在的作用, 可通过表观遗传、转录及转录后水平发挥作用. lncRNAs 已成为继miRNAs 之后的又一重要的调节性非编码RNA. 就非编码RNA 在心脏重构及再生进程中的调控作用进行综述.     

Advances in the study on induced pluripotent stem cells

Recently, the study on ＂induced pluripotent stem cells＂ （iPS cells） has made a great breakthrough, and it is considered as a new milestone in the history of life science. This progress has updated our traditional concepts about pluripotency control, and provided people with a brand-new strategy for somatic cell nuclear reprogramming. In virtue of its availability and stability, this method holds great potential in both biological and clinical research. In order to introduce this rising field of study, this paper starts with an overview of the development of iPS cell establishment, describes the key steps in generating iPS cells, elaborates several relevant scientific issues, and evaluates its current restrictions and promises in future research.     

Induced pluripotent stem cell (iPS) technology: promises and challenges

In 2006, an article published in Cell by Shinya Yamanaka took by surprise the stem cell research community. By performing systematic retroviral transduction of factors enriched in embryonic stem (ES) cells, the authors demonstrated the reprogramming of mouse fibroblasts into an ES cell-like state. These cells, baptized iPS (induced pluripotent stem) cells, were immediately recognized as a ground-breaking discovery. Subsequently, the same authors and other groups reported a similar achievement with human fibroblasts. Two years later, the number of top quality papers on iPS is astonishing, and interest in the scientific community has risen to a fever pitch. But although iPS has the potential to revolutionize Regenerative Medicine, important questions still remain unanswered. Work from multiple laboratories worldwide including ours is focused on deciphering the molecular mechanisms of iPS, and trying to improve the technique to make it suitable for the clinic. In this review article we briefly discuss the past, present and future of iPS, with emphasis on urgent issues to be solved. Supported by the National Nature Science Foundation of China (Grant Nos. 30725012, 30630039 and 90813033), Knowledge Innovation Project of Chinese Academy of Sciences (Grant No. KSCX2-YW-R-48), National Key Basic Research and Development Program of China (Grant Nos. 2006CB701504, 2006CB943600, 2007CB948002, 2007CB947804. 2007CB947900) and Guangzhou Science and Technology Development Funds (Grant No. 2008A1-E4011)     

诱导性多潜能干细胞(iPS)研究：现状与展望

通过特定的基因组合与转染可以将已分化的体细胞诱导重编程为多潜能干细胞（iPS）,是近年来干细胞研究领域最令人瞩目的一项新的干细胞制造技术。与胚胎干细胞（ES）不同,iPS细胞的制造不需要毁损胚胎,因而不会涉及更多的伦理学问题。iPS的出现不仅为体细胞重编程去分化机制的研究注入了新的活力,而且为疾病发生发展相关机制研究与特异的细胞治疗,特别是再生医学带来新的曙光。目前,iPS的研究尚处于初级阶段,文章就iPS的研究现状与应用前景进行综述和展望。     

Nuclear reprogramming by nuclear transplantation and defined transcription factors

In the past ten years, great breakthroughs have been achieved in the nuclear reprogramming area. It has been demonstrated that highly differentiated somatic cell genome could be reprogrammed to a pluripotent state, which indicates that differentiated cell fate is not irreversible. Nuclear transplantation and induced pluripotent stem (iPS) cell generation are the two major approaches to inducing reprogramming of differentiated somatic cell genome. In the present review, we will summarize the recent progress of nuclear reprogramming and further discuss the potential to generate patient specific pluripotent stem cells from differentiated somatic cells for therapeutic purpose. Supported by the National High Technology Research and Development Program of China (Grant No. 2005AA210930)     

Differentiation of human embryonic stem cells along a hepatocyte lineage and its application in liver regeneration

Hepatocyte transplantation and bioarUficial liver （BAL） as alternatives to liver transplantation offer the possibility of effective treatment for many inherited and acquired hepatic disorders. Unfortunately, the limited availability of donated livers and the variability of their derived hepatocytes make it difficult to obtain enough viable human hepatocytes for the hepatocyte-based therapies. Embryonic stem cells （ESCs）, which could be isolated directly from the blastocyst inner cell mass, have permanent self-renewal capability and developmental pluripotency and therefore might be an ideal cell source in the treatment of hepatic discords. However, differentiation of hESCs into hepatocytes with significant numbers remains a challenge. This review updates our current understanding of differentiation of ESCs into hepatic lineage cells, their future therapeutic uses and problems in liver regeneration.     

Therapeutic applications of bone marrow-derived stem cells in liver transplantation for end-stage liver diseases

Today, liver transplantation (LT) is the only established treatment for end-stage liver diseases. The de- velopment of LT, including OLT, cadaveric LT, split LT, living donor LT (LDLT), brings hopes to patients with these diseases. However, increasing donor shortage, rejection and life-long immunosuppression with its side effects are the major limitations of this therapy strategy. Bone marrow-derived stem cells (BMDSCs) are capable of differentiating into hepatocyte-like cells and contribute to liver injury repair. The microenvironment of liver injury caused by rejection, ischemia/reperfusion, loss of liver mass, recurrence of HCV and "small-for-size syndrome" after LT can attract a variety of bone marrow-derived stem cell population to the peripheral circulation and then migration to the injury liver to promote the hepatic function restoration. Additionally, BMDSCs can also take part in the functional regeneration of living donor liver after LDLT. This participation in liver regeneration may be associated to the interac- tion between SDF-1and its receptor CXCR4, involving HGF, IL-8, MMP9, and VEGF/VEGFR-2. BMDSC with its bio-characteristics could maintain the allograft tolerance from different angles and in different ways. In conclusion, BMDSCs transplantation, as a new assistant therapeutic method for LT, will ex- pand the space of LT, and provide more survival opportunities for the patients suffering liver diseases in the future.     

Akt–Oct4 regulatory circuit in pluripotent stem cells

Oct4 is mainly expressed in embryonic stem cells(ESCs),germline stem cells,and embryonal carcinoma cells(ECCs)and plays an indispensable role in maintaining the pluripotency and self-renewal of these pluripotent stem cells.Akt serine/threonine kinase,a wellestablished anti-apoptosis and cell survival factor,has also been implicated as an important regulator of stemness.Emerging evidence indicated that Oct4 is reciprocally connected to Akt via a number of routes,and moreover,a direct interaction between Oct4 and Akt has recently been revealed.These components collectively form the Akt–Oct4 regulatory circuit.In this review,we summarize our current knowledge about the Akt–Oct4 regulatory circuit in ESCs and discuss its alterations in ECCs that may underlie the tumorigenesis of pluripotent stem cells.