Malecki Marek
Stem Cell Res Ther. 2014 Jun 3;5(3):73. doi: 10.1186/scrt462.
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.
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严重的并发症可能是医源性致癌。尽管如此，尽管在诱导多能性和定向分化的新技术开发方面取得了快速进展，但治疗性植入的多能干细胞发生致癌转化的风险仍然存在。“首要的是，不伤害”，正如希波克拉底誓言中所说，是我们的终极信条。因此，在设计任何涉及干细胞的治疗方案时，首要目标应该是消除它们发生肿瘤转化的任何可能性。我在此回顾为实现这一目标而设计的基本策略：用靶向表面展示生物标志物的抗体筛选未分化的多能干细胞；在表达重组蛋白作为报告分子的分化细胞中进行筛选；用毒性抗体或抗体导向毒素杀死未分化的干细胞；用细胞毒性药物消除未分化的干细胞；通过导入自杀诱导基因使潜在致瘤性干细胞对前体药物敏感；通过人重组脱氧核糖核酸酶的自触发转基因表达根除分化抗性干细胞。每一个未分化的多能干细胞都有发生肿瘤转化的风险。因此，上述或其他防止这些干细胞医源性转化的新策略应被考虑纳入每一项干细胞治疗试验中。
