能夠產(chǎn)生任何胎兒或成體細胞類型的人干細胞也被稱作多能性干細胞(pluripotent stem cell),。人們希望這些細胞---它們當中最為著名的是人胚胎干細胞(human embryonic stem cells, hESCs)---能夠被用于產(chǎn)生具有治療用途的細胞群體,。在這種背景下，hESCs產(chǎn)生的神經(jīng)衍生物(neural derivative)正在臨床試驗中接受測試,。然而，法國單基因疾病干細胞治療和探索研究所Natalie Lefort和同事們?nèi)缃癞a(chǎn)生警示性數(shù)據(jù)意味著人們需要實施額外的質(zhì)量控制以便確保人多能性干細胞的神經(jīng)衍生物在基因組上不是不穩(wěn)定的,，而基因組不穩(wěn)定性是癌細胞的一個常見特征,。
Lefort和同事們的關(guān)鍵發(fā)現(xiàn)是人多能性干細胞的神經(jīng)衍生物經(jīng)常性地獲得來自染色體1q的額外物質(zhì)。盡管Lefort和同事們發(fā)現(xiàn)他們檢測到的異常神經(jīng)細胞在小鼠中不能形成腫瘤,，但是讓人擔憂的是,，這種染色體缺陷與一些血細胞癌和兒童腦瘤相關(guān)聯(lián),，這些疾病的臨床治療結(jié)果都不好。
就像英國謝菲爾德大學(xué)Neil Harrison在一篇隨同發(fā)表的評論文章中注意到的那樣,，盡管這些數(shù)據(jù)產(chǎn)生與這些細胞的治療用途相關(guān)的安全問題,，但是事實上在所有的病例中相同的染色體受到影響，意味著人們應(yīng)當可能設(shè)計出篩選策略來檢測和移除這些細胞,。(生物谷：towersimper編譯)
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.
