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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激活和诱导多能干细胞来源的间充质干细胞向多能性的回复。

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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（iPSC）在再生医学和疾病建模中具有巨大潜力。现在认为，应该对衍生自非整合构建体的iPSC进行临床试验。但是，仍在发表许多研究，包括描述疾病模型的研究，这些研究使用的是整合构建物产生的iPSC细胞。我们的实验工作提出了几种细胞类型中体外自发转基因激活的第一个证据。我们的结果表明，转基因在亲本iPSC中主要是沉默的，但是在间充质和内皮iPSC衍生物中，转基因经历了Nanog和c-Myc的随机上调。此外，我们提供了衍生自iPSC的间充质干细胞自发性二次重编程和回复多能性的证据。这些发现强烈表明，研究应使用转基因慢病毒产生的iPSC衍生的细胞产物进行研究，并应考虑转基因重新激活的可能性。这里描述的体外模型提供了对培养物转化的最早事件的洞察力，并提出了一种假设，即在细胞替代实验中，回复多能性可能是肿瘤发展的原因。但是，这项工作的主要目的是传达逆转录-或慢病毒-iPSC衍生物中转基因重新激活的可能性以及相关的体外细胞保真度损失，这可能会影响疾病建模和相关实验的结果。

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