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《中华细胞与干细胞杂志(电子版)》2016,(3)
诱导多能干细胞(iPSC)是通过向已分化成熟的成体细胞转染外源特定的基因重编程而得到的一种类似于胚胎干细胞(ESC)的多潜能干细胞。iPSC克服了ESC临床应用中带来的免疫排斥及伦理问题而具有重要的临床应用价值。iPSC在适当条件下可以实现神经分化,其体外定向分化为运动神经元的研究取得了一定进展。本文就运动神经元的发育、iPSC向运动神经元诱导分化条件、运动神经元鉴定,临床应用及还存在的问题予以综述。 相似文献
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目前细胞和发育生物学上的研究成果为生物医学研究提供了广泛的前景.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,这点燃了再生医学应用的新希望,这一成果从法律、道德、伦理等不同方面被人们所接受.通过体细胞克隆胚胎获得干细胞所面临的破坏胚胎的伦理限制,促使研究者去寻求将分化细胞重编程逆转为干细胞的新方法.主要论述了体细胞重编程的原理、过程及不经过胚胎逆转为多能干细胞的方法. 相似文献
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《现代生物医学进展》2017,(33)
诱导多能干细胞(IPSCs)是通过强制表达多能因子重编程为多潜能的体细胞。这种细胞具有与胚胎干细胞(ESCs)相同的多潜能性,并被认为是有伦理争议的ESCs的替代细胞。然而,使用基因组整合逆转录病毒或慢病毒将细胞重编程成IPSCs的传统方法,通过遗传修饰来重编程IPSCs增加了恶性转化的可能性,并成为其在临床环境中应用的障碍。因此,需要一种替代方法在不使用基因编辑的情况下重编程细胞,并且是通过更安全的方式来传递转录因子以诱导靶细胞上的多能性。许多研究已经证明蛋白转导技术可以通过传递重编程蛋白从人成纤维细胞和小鼠胚胎成纤维细胞产生IPSCs。本文就蛋白转导技术在IPSCs重编程中的应用进展作一综述。 相似文献
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<正>2012年诺贝尔奖生理学或医学奖授予约翰·格登(John Gurdon)和山中伸弥(Shinya Yamanaka),以奖励他们发现了成熟细胞可以被重新编程而具备多潜能性。自此,诱导多能干细胞(iPSC)也变得家喻户晓。细胞重编程是指利用诱导因子,把已分化的细胞恢复为全能或多能干细胞的一种技术。这项技术使得成体细胞"返老还童"为干细胞变 相似文献
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胚胎干细胞不仅是研究哺乳动物早期胚胎发育、细胞分化、基因表达调控等发育生物学问题的有力工具,还可用于新药评价、细胞治疗等方面的研究.然而,为科学研究而捐献的人类卵子并不能够轻易获得,限制了人类胚胎干细胞相关研究的进展,解决这个问题的理想办法就是找到能够替代胚胎干细胞的其他成体多能细胞.综述了将哺乳动物体细胞诱导为多能干细胞的方法,重点介绍了利用特定的转录因子将体细胞诱导为诱导多能干细胞(induced pluripotent stem cells,iPS细胞)的最新进展,详细阐述了转录因子在诱导细胞重编程过程中发挥的作用,以及iPS细胞筛选与鉴定的方法,并展望了iPS细胞的应用前景. 相似文献
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椎间盘退变始发于髓核组织,获得足够有功能的髓核细胞是研究及治疗椎间盘退变的关键.而人诱导多能干细胞(induced pluripotent stem cell,iPSC)不仅为建立疾病模型以研究疾病发生发展机制开辟了道路,还在再生医学领域展现出了广阔的应用前景.我们首先从椎间盘退变患者微创手术获得的髓核组织内分离髓核细胞,将携带OCT3/4、SOX2、KLF4和c-MYC的仙台病毒(Sendai virus,Se V)转染髓核细胞,重编程获得iPSC.通过检测多能细胞特异性标志、体内成瘤实验、甲基化及核型分析对所获得的iPSC进行鉴定.并以皮肤成纤维细胞来源iPSC作为对照,在二维和三维水凝胶中对iPSC进行定向分化,检测髓核细胞相关蛋白和基因的表达,比较分析2种iPSC向髓核细胞的分化效率.结果显示,iPSC能表达多能细胞特异性标志,具有正常的二倍体核型,畸胎瘤实验显示三个胚层的出现.诱导分化后的iPSC表达髓核相关基因和蛋白,在水凝胶中诱导培养后,iPSC表达更多的髓核相关基因和蛋白.髓核来源的iPSC与成纤维细胞来源的iPSC相比,可表达更多的髓核相关基因和蛋白.本研究首次将患者退变髓核细胞重编程成iPSC,并在水凝胶内将其诱导分化为髓核样细胞,为椎间盘退变个体化细胞治疗奠定基础. 相似文献
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生殖细胞的发生是发育和遗传的基础。在几乎所有哺乳动物中,原始生殖细胞(primordial germ cell,PGC)均由近端上胚层体细胞在周边细胞特定的信号诱导下特化而成。目前的研究已经发现一些与生殖细胞特化有关的信号分子和关键转录调控元件,以及特化后生殖细胞获得的与体细胞不同的生物特性。生殖细胞的特化是一个结合了体细胞发育程序的抑制、细胞多能性程序的启动和全基因组表观遗传重编程三个方面的动态的复杂过程。多能性干细胞(胚胎干细胞或诱导型多能干细胞)具有发育全能性,能分化为机体任何一种细胞类型,包括生殖细胞。利用多能性干细胞体外分化形成生殖细胞有助于深入系统地研究配子发生的调控机制,为干细胞在不育症治疗方面的应用带来新希望。 相似文献
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Bharath Kumar Velmurugan Lohanathan Bharathi Priya Paramasivan Poornima Li-Jen Lee Rathinasamy Baskaran 《Journal of cellular physiology》2019,234(6):8443-8454
Engineering/reprogramming differentiated adult somatic cells to gain the ability to differentiate into any type of cell lineage are called as induced pluripotent stem cells (iPSCs). Offering unlimited self-renewal and differentiation potential, these iPSC are aspired to meet the growing demands in the field of regenerative medicine, tissue engineering, disease modeling, nanotechnology, and drug discovery. Biomaterial fabrication with the rapid evolution of technology increased their versatility and utility in regenerative medicine and tissue engineering, revolutionizing the stem cell biology research with the property to guide the process of proliferation, differentiation, and morphogenesis. Combining traditional culture platforms of iPSC with biomaterials aids to overcome the limitations associated with derivation, proliferation, and maturation, thereby could improve the clinical translation of iPSC. The present review discusses in brief about the reprogramming techniques for the derivation iPSC and details on several biomaterial guided differentiation of iPSC to different cell types with specific relevance to tissue engineering/regenerative medicine. 相似文献
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诱导性多能干细胞(induced pluripotent stem cell,iPS cell)是通过转染外源特定的基因组合来诱导成体细胞重编程为类似于胚胎干细胞的一种多潜能干细胞,iPS细胞与胚胎干细胞不仅在形态上相似,而且在功能方面几乎相同.另外,iPS细胞的诞生克服了胚胎干细胞在临床应用时涉及的移植免疫排斥与伦理道德问题,因此具有重要的临床应用价值.目前iPS在治疗中枢神经系统性疾病方面的研究已取得很大进展,包括iPS细胞向神经细胞诱导分化方法的改进、分化机理的探索以及iPS细胞分化来源神经细胞在神经系统疾病模型中治疗作用的研究等.从iPS细胞的创建及特点、iPS细胞向神经细胞分化的诱导方法及研究新进展方面予以综述. 相似文献
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Zhixiang Tong Aniruddh Solanki Allison Hamilos Oren Levy Kendall Wen Xiaolei Yin Jeffrey M Karp 《The EMBO journal》2015,34(8):987-1008
Derived from any somatic cell type and possessing unlimited self-renewal and differentiation potential, induced pluripotent stem cells (iPSCs) are poised to revolutionize stem cell biology and regenerative medicine research, bringing unprecedented opportunities for treating debilitating human diseases. To overcome the limitations associated with safety, efficiency, and scalability of traditional iPSC derivation, expansion, and differentiation protocols, biomaterials have recently been considered. Beyond addressing these limitations, the integration of biomaterials with existing iPSC culture platforms could offer additional opportunities to better probe the biology and control the behavior of iPSCs or their progeny in vitro and in vivo. Herein, we discuss the impact of biomaterials on the iPSC field, from derivation to tissue regeneration and modeling. Although still exploratory, we envision the emerging combination of biomaterials and iPSCs will be critical in the successful application of iPSCs and their progeny for research and clinical translation. 相似文献
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Expression of four major reprogramming transgenes, including Oct4, Sox2, Klf4 and c-myc, in somatic cells enables them to have pluripotency. These cells are iPSC (induced pluripotent stem cell) that currently show the greatest potential for differentiation into cells of the three germ lineages. One of the issues facing the successful reprogramming and clinical translation of iPSC technology is the high rate of apoptosis after the reprogramming process. Reprogramming is a stressful process, and the p53 apoptotic pathway plays a negative role in cell growth and self-renewal. Apoptosis via the p53 pathway serves as a major barrier in nuclear somatic cell reprogramming during iPSC generation. DHEA (dehydroepiandrosterone) is an abundant steroid that is produced at high levels in the adrenal cells, and withdrawal of DHEA increases the levels of p53 in the epithelial and stromal cells, resulting in increased levels of apoptotic cells; meanwhile, DHEA decreases cellular apoptosis. DHEA could improve the efficacy of reprogramming yield due to a decrease in apoptosis via the p53 pathway and an increase in cell viability. 相似文献
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The ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs), exhibiting properties similar to those of embryonic stem cells (ESCs), has attracted much attention, with many studies focused on improving efficiency of derivation and unraveling the mechanisms of reprogramming. Despite this widespread interest, our knowledge of the molecular signaling pathways that are active in iPSCs and that play a role in controlling their fate have not been studied in detail. To address this shortfall, we have characterized the influence of different signals on the behavior of a model mouse iPSC line. We demonstrate significant responses of this iPSC line to the presence of serum, which leads to profoundly enhanced proliferation and, depending on the medium used, a reduction in the capacity of the iPSCs to self-renew. Surprisingly, this iPSC line was less sensitive to withdrawal of LIF compared to ESCs, exemplified by maintenance of expression of a Nanog-GFP reporter and enhanced self-renewal in the absence of LIF. While inhibition of phosphoinositide-3 kinase (PI3K) signaling decreased iPSC self-renewal, inhibition of Gsk-3 promoted it, even in the absence of LIF. High passages of this iPSC line displayed altered characteristics, including genetic instability and a reduced ability to self-renew. However, this second feature could be restored upon inhibition of Gsk-3. Collectively, our data suggest modulation of Gsk-3 activity plays a key role in the control of iPSC fate. We propose that more careful consideration should be given to characterization of the molecular pathways that control the fate of different iPSC lines, since perturbations from those observed in naïve pluripotent ESCs could render iPSCs and their derivatives susceptible to aberrant and potentially undesirable behaviors. 相似文献
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Karina D. Asensi Rodrigo S. Fortunato Danúbia S. dos Santos Thaísa S. Pacheco Danielle F. de Rezende Deivid C. Rodrigues Fernanda C. P. Mesquita Tais H. Kasai‐Brunswick Antonio C. Campos de Carvalho Denise P. Carvalho Adriana B. Carvalho Regina C. dos S. Goldenberg 《Journal of cellular and molecular medicine》2014,18(5):824-831
Properties of induced pluripotent stem cells (iPSC) have been extensively studied since their first derivation in 2006. However, the modification in reactive oxygen species (ROS) production and detoxification caused by reprogramming still needs to be further elucidated. The objective of this study was to compare the response of iPSC generated from menstrual blood–derived mesenchymal stem cells (mb‐iPSC), embryonic stem cells (H9) and adult menstrual blood–derived mesenchymal stem cells (mbMSC) to ROS exposure and investigate the effects of reprogramming on cellular oxidative stress (OS). mbMSC were extremely resistant to ROS exposure, however, mb‐iPSC were 10‐fold less resistant to H2O2, which was very similar to embryonic stem cell sensitivity. Extracellular production of ROS was also similar in mb‐iPSC and H9 and almost threefold lower than in mbMSC. Furthermore, intracellular amounts of ROS were higher in mb‐iPSC and H9 when compared with mbMSC. As the ability to metabolize ROS is related to antioxidant enzymes, we analysed enzyme activities in these cell types. Catalase and superoxide dismutase activities were reduced in mb‐iPSC and H9 when compared with mbMSC. Finally, cell adhesion under OS conditions was impaired in mb‐iPSC when compared with mbMSC, albeit similar to H9. Thus, reprogramming leads to profound modifications in extracellular ROS production accompanied by loss of the ability to handle OS. 相似文献
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Lee DF Su J Ang YS Carvajal-Vergara X Mulero-Navarro S Pereira CF Gingold J Wang HL Zhao R Sevilla A Darr H Williamson AJ Chang B Niu X Aguilo F Flores ER Sher YP Hung MC Whetton AD Gelb BD Moore KA Snoeck HW Ma'ayan A Schaniel C Lemischka IR 《Cell Stem Cell》2012,11(2):179-194
Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A?(Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity?that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming. 相似文献
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诱导多能干细胞(Induced pluripotent stem cells,i PSCs)是利用特定的转录因子诱导体细胞获得的,像胚胎干细胞一样,可以进行无限的自我更新,并具有分化成三个胚层的能力。iPSC有可能提供无限的自体细胞治疗,目前研究已经证实,不同种类疾病的患者提供的成体细胞诱导后可产生种类繁多的iPSC,这项技术给目前无有效治疗手段的多类疾病带来了治疗的希望,并有可能避免利用胚胎干细胞(embryonic stem cells,ESCs)治疗面临的伦理问题和免疫排斥反应。本文回顾iPSC技术优化过程,着重关注应用i PSC建立细胞模型、进行细胞治疗的进展,并探讨iPSC在基础研究及临床应用中遇到的挑战。 相似文献