猪多能干细胞及其分化

T. Ezashi, R. M. Roberts
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摘要

在某些情况下,作为生物医学研究的模型,猪比老鼠更有优势。多能细胞系的可用性可能会扩大这种吸引力。本文综述了猪胚胎干细胞(ESC)和诱导多能系(iPSC)的衍生和鉴定进展。直到最近,大多数猪ESC未能满足多能性的全部标准,但随着对培养条件的了解越来越多,这种情况可能会改变,因为培养条件需要保持早期猪概念的外胚层产物处于未分化、自我更新的状态。此外,猪iPSC细胞已被生成,其中一些具有依赖于fgf2的外胚型细胞的特征,以人ESC为典型,而另一些则需要LIF,类似于“基态”,如ï ve型小鼠ESC。尽管取得了这些成功,但如果要充分发挥多能干细胞的潜力,在选择条件放宽时,不完全的重新编程和多能性的丧失仍然是必须克服的问题。iPSC最直接的价值可能与它们在培养中几乎无限增殖的能力有关,因此可以通过生长选择对基因组进行比其他细胞类型更复杂的遗传操作。iPSC的“未分化”状态也可以提高克隆效率,尽管这还有待证实。最后,猪很可能在测试干细胞疗法中被证明是有用的,尽管只有有限数量的实验证明猪iPSC可以被引导转化为更专门的亚系,然后形成功能性移植物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Porcine pluripotent stem cells and their differentiation
In some situations, the pig has advantages over the mouse as a model in biomedical research. The availability of pluripotent cell lines is likely to broaden this appeal. Here we review progress in the derivation and characterization of embryonic stem cells (ESC) and induced pluripotent lines (iPSC) from pigs. Until recently, most porcine ESC failed to meet the full criteria for pluripotency, but that may be changing as more becomes known about the culture conditions required to maintain epiblast outgrowths from early porcine conceptuses in an undifferentiated, self-renewing state. In addition, porcine iPSC cells have been generated, some with the features of FGF2-dependent epiblast-type cells, typified by human ESC, and others that require LIF and resemble the “ground state”, na ï ve-type mouse ESC. Despite these successes, incomplete reprogramming and loss of pluripotency when selection conditions are relaxed continue to be problems that must be overcome if the full potential of iPSC is to be realized. The most immediate value of iPSC may relate to their ability to proliferate almost indefinitely in culture, thus enabling more complex genetic manipulations of the genome through growth selection than could be performed in other cell types. The “undifferentiated” state of iPSC may also allow improved cloning efficiency, although this remains to be proved. Finally, the pig will likely prove useful in testing stem cell-based therapies, although only a limited number of experiments demonstrating that the porcine iPSC can be directed to transform into more specialized sub-lineages and then form functional grafts have been performed.
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