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首页> 外文期刊>Stem cells and development >Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells
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Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

机译：诱导多能干细胞衍生物中的转基因再激活和抗诱导多能干细胞衍生间充质干细胞多能性的逆转

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摘要

Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retroor lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro-or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation.
机译：诱导多能干细胞（IPSCs）具有巨大的再生医学和疾病建模潜力。现在令人觉醒应使用与非融合结构衍生的IPSC进行临床试验。然而，许多研究包括那些描述疾病模型的研究仍然使用来自综合结构产生的IPSCS的细胞发布。我们的实验工作呈现出几种细胞类型体外自发转基因重新激活的第一证据。我们的结果表明，转基因主要在母体IPSC中沉默，但在间充质和内皮IPSC衍生物中，转基因经历了纳米和C-MYC的随机上调。此外，我们提供了自发次要的重新编程和从IPSC衍生的间充质干细胞中的多能性的逆转证据。这些研究结果强烈建议使用衍生自渗透慢病毒产生的IPSC的细胞产物的研究应考虑到转基因再激活的可能性来评估。这里描述的体外模型提供了对最早的培养转化事件的洞察力，并提出了对多能性逆转的假设可能是对细胞替代实验中肿瘤的发育的原因。然而，这项工作的主要目的是通过体外疾病建模和相关实验的疾病建模和相关实验的结果来传达转基因重新激活的可能性。

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  • 来源
    《Stem cells and development》 |2016年第14期|共13页
  • 作者

    Galat Vasiliy; Galat Yekaterina; Perepitchka Mariana; Jennings Lawrence J.; Iannaccone Philip M.; Hendrix Mary J. C.;

  • 作者单位

    Northwestern Univ Feinberg Sch Med Ann &

    Robert H Lurie Childrens Hosp Chicago Dept Pathol;

    Northwestern Univ Feinberg Sch Med Ann &

    Robert H Lurie Childrens Hosp Chicago Dev Biol Program;

    Northwestern Univ Feinberg Sch Med Ann &

    Robert H Lurie Childrens Hosp Chicago Dev Biol Program;

    Northwestern Univ Feinberg Sch Med Ann &

    Robert H Lurie Childrens Hosp Chicago Dept Pathol;

    Northwestern Univ Feinberg Sch Med Ann &

    Robert H Lurie Childrens Hosp Chicago Dev Biol Program;

    Northwestern Univ Feinberg Sch Med Robert H Lurie Comprehens Canc Ctr Canc Biol &

    Epigen Program;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 基础医学;
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