'Above all, do no harm': safeguarding pluripotent stem cell therapy against iatrogenic tumorigenesis.
'Above all, do no harm': safeguarding pluripotent stem cell therapy against iatrogenic tumorigenesis.
复制标题
DOI：
10.1186/scrt462
复制
发表时间：
2014-06-03
影响因子：
7.5
通讯作者：
Malecki M
中科院分区：
文献类型：
--
作者：
Malecki M
人类多能干细胞是再生医学的基础。然而，在治疗中使用多能干细胞最糟糕的可能并发症可能是医源性癌症发生。然而，尽管诱导多能性和定向分化的新技术开发取得了快速进展，但治疗植入的多能干细胞致癌转化的风险仍然存在。引用希波克拉底誓言的“最重要的是，不要伤害”是我们的终极信条。因此，设计任何涉及干细胞的治疗方案的主要目标应该是消除其肿瘤转化的任何可能性。我在这里回顾的基本策略，已被设计来实现这一目标：分选出未分化的，多能干细胞与抗体靶向表面展示的生物标志物;分选分化的细胞，表达重组蛋白作为报告;杀死未分化的干细胞与有毒抗体或抗体引导的毒素;消除未分化的干细胞与细胞毒性药物;通过用自杀诱导基因转化，使潜在的致瘤干细胞对前药敏感;通过人重组DNA酶的自触发转基因表达，根除分化不敏感的干细胞。每一个多能未分化干细胞都有肿瘤转化的风险。因此，上述或其他新的策略，将防止这些干细胞的医源性转化应考虑纳入每一个干细胞治疗试验。
Human pluripotent stem cells are the foundations of regenerative medicine. However, the worst possible complication of using pluripotent stem cells in therapy could be iatrogenic cancerogenesis. Nevertheless, despite the rapid progress in the development of new techniques for induction of pluripotency and for directed differentiation, risks of cancerogenic transformation of therapeutically implanted pluripotent stem cells still persist. 'Above all, do no harm', as quoted from the Hippocratic Oath, is our ultimate creed. Therefore, the primary goal in designing any therapeutic regimes involving stem cells should be the elimination of any possibilities of their neoplasmic transformation. I review here the basic strategies that have been designed to attain this goal: sorting out undifferentiated, pluripotent stem cells with antibodies targeting surface-displayed biomarkers; sorting in differentiating cells, which express recombinant proteins as reporters; killing undifferentiated stem cells with toxic antibodies or antibody-guided toxins; eliminating undifferentiated stem cells with cytotoxic drugs; making potentially tumorigenic stem cells sensitive to pro-drugs by transformation with suicide-inducing genes; eradication of differentiation-refractive stem cells by self-triggered transgenic expression of human recombinant DNases. Every pluripotent undifferentiated stem cell poses a risk of neoplasmic transformation. Therefore, the aforementioned or other novel strategies that would safeguard against iatrogenic transformation of these stem cells should be considered for incorporation into every stem cell therapy trial.
登录
查看更多内容
影响因子：
2.7
作者：
Knoepfler PS
通讯作者：
Knoepfler PS
影响因子：
5.2
作者：
Choo, Andre B.;Tan, Heng Liang;Yap, Miranda
通讯作者：
Yap, Miranda
影响因子：
4.1
作者：
Lim, Denis Y. X.;Ng, Yi-Han;Wong, Victor V. T.
通讯作者：
Wong, Victor V. T.
影响因子：
9.2
作者：
Eiges, R;Schuldiner, M;Benvenisty, N
通讯作者：
Benvenisty, N
影响因子：
23.9
作者：
Ben-David, Uri;Gan, Qing-Fen;Benvenisty, Nissim
通讯作者：
Benvenisty, Nissim