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多能干细胞的两面性——多能性与致瘤性之间的联系。

The Janus face of pluripotent stem cells--connection between pluripotency and tumourigenicity.

机构信息

In Vitro Differentiation Group, Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, Germany.

出版信息

Bioessays. 2010 Nov;32(11):993-1002. doi: 10.1002/bies.201000065.

Abstract

Pluripotent stem cells have gained special attraction because of their almost unlimited proliferation and differentiation capacity in vitro. These properties substantiate the potential of pluripotent stem cells in basic research and regenerative medicine. Here three types of in vitro cultured pluripotent stem cells (embryonic carcinoma, embryonic stem and induced pluripotent stem cells) are compared in their historical context with respect to their different origin and properties. It became evident that tumourigenicity is an inherent property of pluripotent cells based on p53 down-regulation, expression of tumour-related genes and high telomerase activity that allow unlimited proliferation. In addition, culture-adapted genetic and epigenetic changes may induce tumourigenicity of pluripotent cells. The use of stem cells in regenerative medicine, however, requires non-malignant cell types and strategies that circumvent stages of malignancy.Reprogramming strategies of adult somatic cells that avoid the tumourigenic state of pluripotency may offer alternatives for future biomedical application.

摘要

多能干细胞因其在体外几乎无限的增殖和分化能力而备受关注。这些特性使多能干细胞在基础研究和再生医学中有很大的应用潜力。本文将胚胎癌细胞、胚胎干细胞和诱导多能干细胞这三种不同来源和特性的体外培养多能干细胞进行了比较。结果表明,多能细胞的致瘤性是其内在特性,其依据是 p53 下调、肿瘤相关基因的表达和高端粒酶活性,这些特性允许细胞无限制的增殖。此外,适应培养的遗传和表观遗传改变可能会诱导多能细胞的致瘤性。然而,在再生医学中使用干细胞需要非恶性细胞类型和避免恶性阶段的策略。避免多能性致瘤状态的成体细胞重编程策略可能为未来的生物医学应用提供替代方案。

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