UQ Centre for Clinical Research, University of Queensland, Herston campus, Brisbane 4029, Australia.
Stem Cell Rev Rep. 2013 Aug;9(4):408-21. doi: 10.1007/s12015-011-9336-5.
Mesenchymal stem cells (MSC) from fetal-placental tissues have translational advantages over their adult counterparts, and have variably been reported to express pluripotency markers. OCT-4 expression in fetal-placental MSC has been documented in some studies, paradoxically without tumourogenicity in vivo. It is possible that OCT-4 expression is insufficient to induce true "stemness", but this issue is important for the translational safety of fetal-derived MSC. To clarify this, we undertook a systematic literature review on OCT-4 in fetal or adnexal MSC to show that most studies report OCT-4 message or protein expression, but no study provides definitive evidence of true OCT-4A expression. Discrepant findings were attributable not to different culture conditions, tissue sources, or gestational ages but instead to techniques used. In assessing OCT-4 as a pluripotency marker, we highlight the challenges in detecting the correct OCT-4 isoform (OCT-4A) associated with pluripotency. Although specific detection of OCT-4A mRNA is achievable, it appears unlikely that any antibody can reliably distinguish between OCT-4A and the pseudogene OCT-4B. Finally, using five robust techniques we demonstrate that fetal derived-MSC do not express OCT-4A (or by default OCT-4B). Reports suggesting OCT-4 expression in fetal-derived MSC warrant reassessment, paying attention to gene and protein isoforms, pseudogenes, and antibody choice as well as primer design. Critical examination of the OCT-4 literature leads us to suggest that OCT-4 expression in fetal MSC may be a case of "The Emperor's New Clothes" with early reports of (false) positive expression amplified in subsequent studies without critical attention to emerging refinements in knowledge and methodology.
胎儿胎盘组织中的间充质干细胞 (MSC) 比其成人对应物具有翻译优势，并且已经有报道称其表达多能性标志物。在一些研究中已经记录了胎儿胎盘 MSC 中的 OCT-4 表达，但其在体内没有致瘤性，这是矛盾的。OCT-4 表达可能不足以诱导真正的“干性”，但这个问题对于胎儿来源的 MSC 的转化安全性很重要。为了澄清这一点，我们对胎儿或附件 MSC 中的 OCT-4 进行了系统的文献综述，结果表明，大多数研究报告了 OCT-4 信使 RNA 或蛋白表达，但没有研究提供真正的 OCT-4A 表达的明确证据。不一致的发现不是由于不同的培养条件、组织来源或胎龄，而是由于使用的技术不同。在评估 OCT-4 作为多能性标志物时，我们强调了检测与多能性相关的正确 OCT-4 同工型 (OCT-4A) 的挑战。虽然可以实现 OCT-4A mRNA 的特异性检测，但似乎没有任何抗体能够可靠地区分 OCT-4A 和假基因 OCT-4B。最后，我们使用五种稳健的技术证明胎儿来源的 MSC 不表达 OCT-4A（或默认表达 OCT-4B）。关于胎儿来源的 MSC 中 OCT-4 表达的报告需要重新评估，注意基因和蛋白同工型、假基因以及抗体选择和引物设计。对 OCT-4 文献的批判性检查使我们建议，胎儿 MSC 中的 OCT-4 表达可能是“皇帝的新衣”的一个例子，早期的（虚假）阳性表达报告在随后的研究中被放大，而没有对知识和方法学的新进展进行批判性关注。
