Li Qing, Fan Yong, Sun Xiaofang, Yu Yanhong
Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangdong, China.
J Reprod Dev. 2013;59(1):72-7. doi: 10.1262/jrd.2012-109. Epub 2012 Nov 9.
The ectopic expression of transcription factors for reprogramming human somatic cells to a pluripotent state represents a valuable resource for the development of in vitro-based models for human disease and has great potential in regenerative therapies. However, the majority of studies have used skin fibroblasts to generate induced pluripotent stem cells (iPSCs) that typically require the enforced expression of several transcription factors, thereby posing a mutagenesis risk by the insertion of viral transgenes. To reduce this risk, iPSCs have been generated with OCT4 and KLF4 from human neural stem cells that endogenously express the remaining reprogramming factors. However, human neural stem cells are rare and difficult to obtain. Here, we show that iPSCs can be generated from human amniotic fluid cells (hAFCs) with two transcription factors: OCT4 and KLF4. Furthermore, iPSCs can be readily derived from hAFCs in a feeder-free conditions, thereby eliminating the potential variability caused by using feeder cells. Our results indicate that hAFCs represent an accessible source of cells that can be reprogrammed into pluripotent stem cells with two Yamanaka factors. Therefore, hAFCs may become a preferred cell type in the future for safe reprogramming without any exogenous genetic material.
将人类体细胞重编程为多能状态的转录因子的异位表达，是开发基于体外的人类疾病模型的宝贵资源，在再生疗法中具有巨大潜力。然而，大多数研究使用皮肤成纤维细胞来生成诱导多能干细胞（iPSC），这通常需要强制表达几种转录因子，从而因病毒转基因的插入而带来诱变风险。为降低这种风险，已利用人神经干细胞中的OCT4和KLF4生成了iPSC，这些神经干细胞内源性表达其余的重编程因子。然而，人神经干细胞稀少且难以获得。在此，我们表明，使用两种转录因子OCT4和KLF4可从人羊水细胞（hAFC）生成iPSC。此外，可在无饲养层条件下轻松从hAFC获得iPSC，从而消除使用饲养细胞引起的潜在变异性。我们的结果表明，hAFC是一种可获取的细胞来源，可用两种山中因子将其重编程为多能干细胞。因此，hAFC未来可能成为无需任何外源性遗传物质即可进行安全重编程的首选细胞类型。
