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用自杀基因保护非人类灵长类动物的 iPS 细胞。

Safeguarding nonhuman primate iPS cells with suicide genes.

机构信息

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA.

出版信息

Mol Ther. 2011 Sep;19(9):1667-75. doi: 10.1038/mt.2011.51. Epub 2011 May 17.

DOI:10.1038/mt.2011.51
PMID:21587213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3182363/
Abstract

The development of technology to generate induced pluripotent stem (iPS) cells constitutes one of the most exciting scientific breakthroughs because of the enormous potential for regenerative medicine. However, the safety of iPS cell-related products is a major concern for clinical translation. Insertional mutagenesis, possible oncogenic transformation of iPS cells or their derivatives, or the contamination of differentiated iPS cells with undifferentiated cells, resulting in the formation of teratomas, have remained considerable obstacles. Here, we demonstrate the utility of suicide genes to safeguard iPS cells and their derivatives. We found suicide genes can control the cell fate of iPS cells in vitro and in vivo without interfering with their pluripotency and self-renewal capacity. This study will be useful to evaluate the safety of iPS cell technology in a clinically highly relevant, large animal model and further benefit the clinical use of human iPS cells.

摘要

诱导多能干细胞(iPS)技术的发展是最令人兴奋的科学突破之一,因为它具有巨大的再生医学潜力。然而,iPS 细胞相关产品的安全性是临床转化的主要关注点。插入突变、iPS 细胞或其衍生物的可能致癌转化,或分化的 iPS 细胞被未分化细胞污染,导致畸胎瘤的形成,仍然是相当大的障碍。在这里,我们证明了自杀基因在保护 iPS 细胞及其衍生物方面的效用。我们发现自杀基因可以在不干扰 iPS 细胞多能性和自我更新能力的情况下,控制 iPS 细胞在体外和体内的细胞命运。这项研究将有助于在临床高度相关的大动物模型中评估 iPS 细胞技术的安全性,并进一步促进人类 iPS 细胞的临床应用。

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本文引用的文献

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Efficient generation of nonhuman primate induced pluripotent stem cells.高效生成非人灵长类动物诱导多能干细胞。
Stem Cells Dev. 2011 May;20(5):795-807. doi: 10.1089/scd.2010.0343. Epub 2011 Feb 1.
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Death switch for gene therapy: application to erythropoietin transgene expression.基因治疗的死亡开关:应用于促红细胞生成素转基因表达。
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The growth of brain tumors can be suppressed by multiple transplantation of mesenchymal stem cells expressing cytosine deaminase.间质干细胞表达胞嘧啶脱氨酶多次移植可抑制脑瘤生长。
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Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders.健康供者和获得性血液疾病患者血细胞诱导的多能干细胞。
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Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases.利用锌指核酸酶有效靶向人类胚胎干细胞和诱导多能干细胞中的表达基因和沉默基因。
Nat Biotechnol. 2009 Sep;27(9):851-7. doi: 10.1038/nbt.1562. Epub 2009 Aug 13.