Back and forth in time: Directing age in iPSC-derived lineages.
Back and forth in time: Directing age in iPSC-derived lineages.
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DOI：
10.1016/j.brainres.2015.11.013
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发表时间：
2017-02-01
期刊：
影响因子：
2.9
通讯作者：
Studer L
中科院分区：
文献类型：
--
作者：
Cornacchia D;Studer L
诱导多能干细胞(IPSC)的出现改变了研究人类疾病的经典方法，为研究疾病发病机制和药物筛选提供了从患者体内获取疾病相关细胞的体外途径。然而，尽管近年来开发了大量基于ipsc的疾病模型，但越来越多的证据表明，这项技术可能并不完全适合研究老年条件，如神经退行性变。在多能起源的细胞中概括疾病的晚期特征的困难被认为是IPSC子代的胎儿样本质与神经退行性综合征发病的高龄之间的差异。除了已知会影响多能细胞衍生品的功能不成熟问题外，最新的发现表明，重新编程也会使细胞经历一个“年轻”的过程，导致细胞太“年轻”而不能表现出与年龄相关的疾病的表型。因此，随着在操纵细胞命运方面取得重大进展，干细胞领域现在将不得不面临控制细胞年龄的新挑战，以充分利用IPSC技术的潜力来推进脑老化疾病的研究和治疗。
The advent of induced pluripotent stem cells (iPSC) has transformed the classic approach of studying human disease, providing in vitro access to disease-relevant cells from patients for the study of disease pathogenesis and for drug screening. However, in spite of the broad repertoire of iPSC-based disease models developed in recent years, increasing evidence suggests that this technology might not be fully suitable for the study of conditions of old age, such as neurodegeneration. The difficulty in recapitulating late-stage features of disease in cells of pluripotent origin is believed to be a discrepancy between the fetal-like nature of iPSC-progeny and the advanced age of onset of neurodegenerative syndromes. In parallel to the issue of functional immaturity known to affect derivatives of pluripotent cells, latest findings suggest that reprogramming also subjects cells to a process of “rejuvenation”, giving rise to cells that are too “young” to manifest phenotypes of age-related diseases. Thus, following the significant progress in manipulating cellular fate, the stem cell field will now have to face the new challenge of controlling cellular age, in order to fully harness the potential of iPSC-technology to advance the research and cure of diseases of the aging brain.