A Scalable Approach to Prevent Teratoma Formation of Human Embryonic Stem Cells
A Scalable Approach to Prevent Teratoma Formation of Human Embryonic Stem Cells
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DOI：
10.1074/jbc.m112.383810
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发表时间：
2012-09-21
影响因子：
4.8
通讯作者：
Xu, Yang
中科院分区：
文献类型：
--
作者：
Rong, Zhili;Fu, Xuemei;Xu, Yang
作为体内所有细胞类型的可再生来源，人类胚胎干细胞（hESCs）在人类细胞治疗方面前景广阔。然而，阻碍hESCs临床应用的一个主要瓶颈是hESCs在移植后仍然具有分化衍生物，通过形成畸胎瘤而具有癌症风险。NANOG是一种重要的多能性因子，在hESC中特异性表达，但很少在其分化的衍生物中表达。通过同源重组将单纯疱疹病毒胸苷激酶基因的高活性变体引入hESC内源性NANOG基因的3 '非翻译区，我们开发了一种安全且高度可扩展的方法，以有效消除与hESC相关的畸胎瘤风险，而不会对其分化的细胞类型产生明显的负面影响。由于胸苷激酶广泛应用于人类基因治疗试验，是美国的治疗靶点。S.食品和药物管理局批准的药物，我们的策略可以有效地应用于临床开发的hESC为基础的人类细胞治疗。
As the renewable source of all cell types in the body, human embryonic stem cells (hESCs) hold great promise for human cell therapy. However, one major bottleneck that hinders the clinic application of hESCs is that hESCs remaining with their differentiated derivatives pose cancer risk by forming teratomas after transplantation. NANOGis a critical pluripotency factor specifically expressed in hESCs but rarely in their differentiated derivatives. By introducing a hyperactive variant of herpes simplex virus thymidine kinase gene into the 3'-untranslated region of the endogenous NANOG gene of hESCs through homologous recombination, we developed a safe and highly scalable approach to efficiently eliminate the teratoma risk associated with hESCs without apparent negative impact on their differentiated cell types. As thymidine kinase is widely used in human gene therapy trials and is the therapeutic target of U. S. Food and Drug Administration-approved drugs, our strategy could be effectively applied to the clinic development of hESC-based human cell therapy.