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Induced pluripotent stem cells:opportunities and challenges

机译:诱导多能干细胞:机遇与挑战

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摘要

Somatic cells have been reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors, such as Oct3/4, Sox2, Klf4 and c-Myc. Induced pluripotent stem (iPS) cells from a patient’s somatic cells could be a useful source for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into the host genomes and may increase the risk of tumour formation. Several non-integration methods have been reported to overcome the safety concern associated with the generation of iPS cells, such as transient expression of the reprogramming factors using adenovirus vectors or plasmids, and direct delivery of reprogramming proteins. Although these transient expression methods could avoid genomic alteration of iPS cells, they are inefficient. Several studies of gene expression, epigenetic modification and differentiation revealed the insufficient reprogramming of iPS cells, thus suggesting the need for improvement of the reprogramming procedure not only in quantity but also in quality. This report will summarize the current knowledge of iPS generation and discuss future reprogramming methods for medical application.
机译:通过引入几种转录因子(例如Oct3 / 4,Sox2,Klf4和c-Myc)的组合,体细胞已被重新编程为多能干细胞。来自患者体细胞的诱导多能干(iPS)细胞可能是药物发现和细胞移植疗法的有用来源。但是,大多数人iPS细胞是由病毒载体(如逆转录病毒和慢病毒)制成的,它们将重编程因子整合到宿主基因组中,并可能增加肿瘤形成的风险。已报道了几种非整合方法来克服与iPS细胞生成相关的安全问题,例如使用腺病毒载体或质粒瞬时表达重编程因子,以及直接递送重编程蛋白。尽管这些瞬时表达方法可以避免iPS细胞的基因组改变,但效率低下。基因表达,表观遗传修饰和分化的一些研究表明,iPS细胞的重编程不足,因此,不仅需要在数量上而且在质量上都需要改进重编程程序。该报告将总结iPS生成的当前知识,并讨论医疗应用的未来重编程方法。

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