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本帖最后由 细胞海洋 于 2010-12-3 22:16 编辑 ) M4 V$ W% q6 G4 M; U
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Human embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro†4 m* _2 w( {5 d. a3 H# L8 l5 G
Keywords:
* l, P* m# J; D) Jprions;stem cells;Creutzfeldt-Jakob disease (CJD);BSE;prion protein (PrP);cell culture;iatrogenic transmission n' C/ ]; L k0 U
Abstract; t' r$ K& p2 G# g% A2 n
Susceptibility to prion infection involves interplay between the prion strain and host genetics, but expression of the host-encoded cellular prion protein is a known pre-requisite. Here we consider human embryonic stem cell (hESC) susceptibility by characterising the genetics and expression of the normal cellular prion protein and by examining their response to acute prion exposure. Seven hESC lines were tested for their prion protein gene codon 129 genotype and this was found to broadly reflect that of the normal population. hESCs expressed prion protein mRNA, but only low levels of prion protein accumulated in self-renewing populations. Following undirected differentiation, upregulation of prion protein expression occurred in each of the major embryonic lineages. Self-renewing populations of hESCs were challenged with infectious human and animal prions. The exposed cells rapidly and extensively took up this material, but when the infectious source was removed the level and extent of intracellular disease-associated prion protein fell rapidly. In the absence of a sufficiently sensitive test for prions to screen therapeutic cells, and given the continued use of poorly characterised human and animal bioproducts during hESC derivation and cultivation, the finding that hESC rapidly take up and process abnormal prion protein is provocative and merits further investigation. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.( k5 H6 a5 B9 x* x9 M: A
阮病毒感染的敏感性一定程度上取决于阮病毒毒力和宿主遗传特性之间的相互作用，但是表达宿主编码的阮蛋白是已知的先决条件。在我们的研究中我们通过了解人类胚胎干细胞的遗传特征、让其表达正常细胞的朊蛋白、监测其被急性感染阮病毒后的反应来了解人类胚胎干细胞对于阮病毒的敏感性。选取7株细胞系测试他们的阮蛋白基因密码子129基因型，这能大致反映正常人群的情况。hESCs转录了阮蛋白的mRNA，但是在自我更新的细胞中只有低水平的阮蛋白积累。在不定向分化过程中，大多数细胞系中的阮蛋白出现上调现象。自我更新过程中的hESCs面临着来自人类和动物的阮病毒的挑战（将来自人类和动物的阮病毒接种hESCs中）。接触阮病毒的细胞很快就吸收了这些“病毒蛋白”，但是当移除传染源后细胞内病毒相关的阮蛋白迅速下降。
% ^$ G2 @6 H# \3 u/ d# H对于阮病毒缺乏一种有效的敏感性试验用于筛选治疗性的细胞，以及鉴于在hESC培养和诱导过程中持续使用了解较少的人类和动物性生物产品， 这个发现即hESC 能够迅速接受并处理异常朊蛋白是具有未来深入研究的价值的。, T2 \9 g; i2 e g, w9 g0 B
http://onlinelibrary.wiley.com/doi/10.1002/path.2832/abstract
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发表于 2010-12-3 15:55
发表于 2010-12-3 18:31
挺好的
