能够产生任何胎儿或成体细胞类型的人干细胞也被称作多能性干细胞(pluripotent stem cell)。人们希望这些细胞---它们当中最为著名的是人胚胎干细胞(human embryonic stem cells, hESCs)---能够被用于产生具有治疗用途的细胞群体。在这种背景下，hESCs产生的神经衍生物(neural derivative)正在临床试验中接受测试。然而，法国单基因疾病干细胞治疗和探索研究所Natalie Lefort和同事们如今产生警示性数据意味着人们需要实施额外的质量控制以便确保人多能性干细胞的神经衍生物在基因组上不是不稳定的，而基因组不稳定性是癌细胞的一个常见特征。
Lefort和同事们的关键发现是人多能性干细胞的神经衍生物经常性地获得来自染色体1q的额外物质。尽管Lefort和同事们发现他们检测到的异常神经细胞在小鼠中不能形成肿瘤，但是让人担忧的是，这种染色体缺陷与一些血细胞癌和儿童脑瘤相关联，这些疾病的临床治疗结果都不好。
就像英国谢菲尔德大学Neil Harrison在一篇随同发表的评论文章中注意到的那样，尽管这些数据产生与这些细胞的治疗用途相关的安全问题，但是事实上在所有的病例中相同的染色体受到影响，意味着人们应当可能设计出筛选策略来检测和移除这些细胞。(生物谷：towersimper编译)
doi:10.1172/JCI46268
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Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells
Christine Varela, Jérôme Alexandre Denis, Jérôme Polentes, Maxime Feyeux, Sophie Aubert, Benoite Champon, Geneviève Piétu, Marc Peschanski and Nathalie Lefort
Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines.
doi:10.1172/JCI62002
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Genetic instability in neural stem cells: an inconvenient truth?
Neil J. Harrison
The evolutionary struggles from which mutants arise have been documented in almost every living system. In this issue of the JCI, Varela and colleagues extend this list of systems to include neural derivatives of human embryonic stem cells, which they show exhibit a repeated gain of material from chromosome 1q. Although this raises safety issues for therapeutic use of such cells, the frequent observation of a particular change may direct screening strategies for detection and removal of these unwanted cellular variants.
