Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state
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DOI：
10.1101/gad.173922.111
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发表时间：
2011-11-01
影响因子：
10.5
通讯作者：
Lemaitre, Jean-Marc
中科院分区：
文献类型：
--
作者：
Lapasset, Laure;Milhavet, Ollivier;Lemaitre, Jean-Marc
将体细胞直接重编程为诱导多能干细胞 (iPSC) 提供了一个独特的机会来获得患者特异性干细胞，该干细胞在组织替代疗法中具有潜在的应用，并且没有人胚胎干细胞 (hESC) 的伦理问题。然而，导致衰老和寿命受限的细胞衰老被描述为 iPSC 衍生的障碍。在这里，我们使用优化的方案证明，细胞衰老并不是重编程的限制，并且与年龄相关的细胞生理学是可逆的。因此，我们表明，由衰老和百岁老人细胞产生的 iPSC 已重置端粒大小、基因表达谱、氧化应激和线粒体代谢，并且与 hESC 没有区别。最后，我们证明衰老和百岁老人衍生的多能干细胞能够重新分化为完全恢复活力的细胞。这些结果为 iPSC 技术提供了新的见解，并为老年患者的再生医学铺平了道路。
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a unique opportunity to derive patient-specific stem cells with potential applications in tissue replacement therapies and without the ethical concerns of human embryonic stem cells (hESCs). However, cellular senescence, which contributes to aging and restricted longevity, has been described as a barrier to the derivation of iPSCs. Here we demonstrate, using an optimized protocol, that cellular senescence is not a limit to reprogramming and that age-related cellular physiology is reversible. Thus, we show that our iPSCs generated from senescent and centenarian cells have reset telomere size, gene expression profiles, oxidative stress, and mitochondrial metabolism, and are indistinguishable from hESCs. Finally, we show that senescent and centenarian-derived pluripotent stem cells are able to redifferentiate into fully rejuvenated cells. These results provide new insights into iPSC technology and pave the way for regenerative medicine for aged patients.