Protecting against wayward human induced pluripotent stem cells with a suicide gene
Protecting against wayward human induced pluripotent stem cells with a suicide gene
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防止带有自杀基因的任性人类诱导多能干细胞
DOI：
10.1016/j.biomaterials.2012.01.023
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发表时间：
2012-04-01
期刊：
影响因子：
14
通讯作者：
Xiang, Andy Peng
中科院分区：
文献类型：
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作者：
Cheng, Fuyi;Ke, Qiong;Xiang, Andy Peng
人类诱导多能干细胞（hiPSCs）的产生为再生医学开辟了前景。然而，来自hiPSC的体细胞的移植仍然存在许多风险，例如细胞的不正确分化或过度增殖，以及最坏的，肿瘤形成。因此，在其临床应用之前，必须解决这些障碍。在此，我们用Ef 1 alpha或Nanog启动子驱动的截短型单纯疱疹病毒δ胸苷激酶（deltaTK）基因对hiPSC和人胚胎干细胞（hECs）进行遗传修饰，以选择性消融任性的多能干细胞。结果表明，deltaTK基因的插入并没有改变它们的多能性和自我更新能力，但使它们对更昔洛韦敏感，更昔洛韦在体外以剂量和时间依赖的方式诱导deltaTK（+）细胞的消除，最重要的是，促进体内肿瘤的预防和消融。此外，转导的hiPSC和hESC之间的比较分析显示它们之间的更昔洛韦敏感性没有差异。这种方法可能有助于为将来hiPSCs在再生医学中的临床应用制定安全策略。(c)2012爱思唯尔有限公司保留所有权利。
The generation of human induced pluripotent stem cells (hiPSCs) opens a prospect for regenerative medicine. However, transplantation of somatic cells derived from hiPSCs still harbor many risks such as cells' incorrect differentiation or over-proliferation, and the worst, tumor formation. Therefore, it's essential to ravel out these obstacles before their clinical application. Herein, we genetically modified hiPSCs and human embryonic stem cells (hESCs) with a truncated herpes simplex virus delta thymidine kinase (deltaTK) gene driven by Ef1 alpha or Nanog promoter to selectively ablate wayward pluripotent stem cells. The results showed that insertion of deltaTK gene did not alter their pluripotency and self-renewal capacity but rendered them sensitive to ganciclovir, which induced elimination of deltaTK(+) cells in vitro in a dose and time-dependent manner, most importantly, facilitated both prevention and ablation of tumors in vivo. Furthermore, comparative analysis between transduced hiPSCs and hESCs showed that there was no difference in ganciclovir sensitivity between them. This approach may help to develop safety strategies for clinical application of hiPSCs in regenerative medicine in the future. (c) 2012 Elsevier Ltd. All rights reserved.