Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells.

Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells.
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DOI:
10.1186/s13045-014-0050-z
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发表时间:
2014-07-19
影响因子:
28.5
通讯作者:
Zhou J
Zhou J
中科院分区:
医学1区
文献类型:
--
作者:
Li J;Song W;Pan G;Zhou J

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成功地将体细胞重编程为多能状态产生诱导多能干细胞(iPS)(或iPSC),其具有像胚胎干细胞(ESC)一样的广泛自我更新能力。iPSC还可以产生子细胞,子细胞可以进一步分化成各种谱系或终末分化以达到其最终功能状态。如何产生iPSCs的发现开辟了干细胞研究的新领域,具有智力和治疗益处。疾病特异性或患者特异性iPSCs的巨大潜在意义促使科学家们解决阻碍其在临床医学中应用的问题,特别是便利性和安全性问题。为了确定适合重编程的组织类型的范围以及它们的特定特征,已经评估了来自三个胚胎胚层的细胞,并且已经阐明了一些组织来源在效率和可及性方面优于成纤维细胞来源的优势。为了以有效和方便的方式提供安全的iPSC,除了努力寻找更好的供体细胞外,还显着改进了诱导因子的递送系统和组合以及用于产生iPSC的化学品。目前,可以在没有c-Myc和Klf 4癌基因的情况下产生iPSC,并且已经成功地采用了非病毒递送无整合的化学介导的重编程方法,其效率相对令人满意。本文将通过强调iPSC的组织来源和生成来综述iPS技术的最新进展。最后讨论了iPSCs在临床应用中需要克服的障碍。
Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.
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