Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach.
Valproic acid confers functional pluripotency to human amniotic fluid stem cells in a transgene-free approach.
复制标题
DOI：
10.1038/mt.2012.117
复制
发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
具有治疗应用潜力的诱导多能干细胞（iPSC）可以通过一组有限且确定的转录因子的异位表达从体细胞衍生。然而，由于重编程转基因随机整合到宿主基因组中的风险、该过程的低效率以及病毒诱导的致瘤性的潜在风险，已经开发了替代方法来使用非整合系统产生多能细胞，尽管成功有限。在这里，我们表明，c-KIT+人早孕期羊水干细胞（AFSC）可以完全重编程为多能性，没有异位因素，培养基质胶在人胚胎干细胞（hESC）培养基补充组蛋白去乙酰化酶抑制剂（HDACi）丙戊酸（VPA）。这些细胞与hESC具有82%的转录组同一性，并且能够在体外形成胚状体（EB）和在体内形成畸胎瘤。在长期扩增后，它们保持遗传稳定性、关键多能性因子的蛋白质水平表达、高细胞分裂动力学、端粒酶活性、X失活的抑制以及分化成三个胚层的谱系（例如定形内胚层、肝细胞、骨、脂肪、软骨、神经元和少突胶质细胞）的能力。我们的结论是，AFSC可用于细胞库的患者特异性多能细胞的潜在应用在同种异体细胞替代疗法，药物筛选，疾病建模。
Induced pluripotent stem cells (iPSCs) with potential for therapeutic applications can be derived from somatic cells via ectopic expression of a set of limited and defined transcription factors. However, due to risks of random integration of the reprogramming transgenes into the host genome, the low efficiency of the process, and the potential risk of virally induced tumorigenicity, alternative methods have been developed to generate pluripotent cells using nonintegrating systems, albeit with limited success. Here, we show that c-KIT+ human first-trimester amniotic fluid stem cells (AFSCs) can be fully reprogrammed to pluripotency without ectopic factors, by culture on Matrigel in human embryonic stem cell (hESC) medium supplemented with the histone deacetylase inhibitor (HDACi) valproic acid (VPA). The cells share 82% transcriptome identity with hESCs and are capable of forming embryoid bodies (EBs) in vitro and teratomas in vivo. After long-term expansion, they maintain genetic stability, protein level expression of key pluripotency factors, high cell-division kinetics, telomerase activity, repression of X-inactivation, and capacity to differentiate into lineages of the three germ layers, such as definitive endoderm, hepatocytes, bone, fat, cartilage, neurons, and oligodendrocytes. We conclude that AFSC can be utilized for cell banking of patient-specific pluripotent cells for potential applications in allogeneic cellular replacement therapies, pharmaceutical screening, and disease modeling.
登录
查看更多内容
影响因子：
1.6
作者：
Galende, Elisa;Karakikes, Ioannis;Polgar, Katalin
通讯作者：
Polgar, Katalin
影响因子：
4.8
作者：
Hezroni, Hadas;Sailaja, Badi Sri;Meshorer, Eran
通讯作者：
Meshorer, Eran
影响因子：
5.2
作者：
Kerr, Candace L.;Hill, Christine M.;Gearhart, John D.
通讯作者：
Gearhart, John D.
影响因子：
6
作者：
Chen, Yen Shun;Pelekanos, Rebecca A.;Fisk, Nicholas M.
通讯作者：
Fisk, Nicholas M.
影响因子：
3.5
作者：
Li, Chunliang;Zhou, Junmei;Jin, Ying
通讯作者：
Jin, Ying