STAP细胞：是真或是假？

上周，中国香港中文大学Kenneth Lee说他将在博客中说自己的小组已经成功重复出日本美国学者合作发表的STAP细胞，这一新发现最近已经成为国际学术领域的重大热点。而此前，也是Kenneth Lee发文称，无法重复小保方睛子的实验。

4 月1日日本理化研究所还公布了最后针对论文伪造数据的调查结论，证明论文第一作者小保方晴子属于学术不端，并对该学者非常不诚实和混乱的研究数据管理表示 吃惊，虽然小保方晴子对这一认证不服，但大量的证据表明确实存在严重的学术不端问题。不过其中关于论文发现的核心，就是所谓酸处理诱导干细胞的技术是否真 实一直无法确认，但论文另一通讯作者，小保方晴子在美国哈弗大学医学院的老板Charles Vacanti一直坚持认为他们的研究结果可靠，并公布了自己的研究技术方案。虽然国际上大量学者对这一研究进行重复，总没有学者公开承认结果符合。不过 最后终于有了例外，来自中国香港中文大学的Kenneth Lee或许成为救美英雄(他们开始也没有重复出结果，其消息被许多大型媒体引用无法重复的证据。

Lee 教授正是利用Vacanti公布的技术方案，重复出STAP细胞。在ResearchGate上，他提供了来自他们实验室转基因成纤维细胞的共聚焦和 qPCR分析数据，这些是细胞经过机械挤压和酸处理后3天的结果。研究过程中第一天，他们发现这些处理后的细胞发生大量死亡，本来他们预期会有越来越多细 胞坏死发生，但是在第三天，结果出现了，这正是Vacanti在报告中描述的关键时间。

4 月1日，Lee公布了他们小组对处理后三天的细胞qPCR分析数据，结果发现，单纯机械压力处理就可以让这些细胞高水平表达Oct4，这是一种诱导干细胞 典型的调节因子，比较神奇的是，这种因子表达水平不仅比对照组高，而且也高于机械压力和酸联合处理的细胞。Lee教授对这些qPCR结果表示十分震惊。

但是，另外一些ResearchGate的评论者对这一结果提出疑问，是否这些结果是因为自发荧光导致的误差。来自俄罗斯科学院的Sergey Kiselev对此大加讽刺，认为这是典型的愚人节笑话。
与STAP相关的拓展阅读：

• STAP细胞：是真或是假？
• Nature：美女科学家STAP干细胞论文伪造“铁证如山”
• Science：聚光灯下刺眼的STAP细胞
• STAP细胞：查尔斯教授强势的理由
• “STAP事件”也许将“峰回路转”
• 理研从主页上删除STAP细胞相关报道
• 综述：日本STAP细胞论文存重大问题
• 调查发现STAP论文图像与小保方晴子博士论文相同
• 小保方晴子有意撤回STAP细胞论文
更多信息请点击：有关STAP更多资讯

还有一些评论：
Shinsakan
Great points. The continued media sensationalism is ironic because I believe that media outlets, especially those in Japan, actually bear some culpability for the magnitude of the STAP debacle in the first place through their inaccurate and sensationalist reporting. When the STAP papers were initially published, the media (especially in Japan) heralded it as a Nobel-level advance, game-changing, paradigm-shifting, “epoch-making” (in the actual words of the Asahi Shimbun), etc, which was a huge exaggeration, even before we knew about all of the problems with the paper. The truly “epoch-making” concept of cellular reprogramming had already been established and the clinical relevance of STAP was questionable, as STAP was suggested to only work in neonatal cells, and even if the initial findings were replicable there was no evidence that it would work in less resilient adult cells or that that the generated STAP stem cells would be healthy or even “safer than iPS cells” as claimed. Most media reports ignored or minimized all of these aspects. Dr. Yamanaka’s recent complaint to RIKEN further highlighted that STAP (if it actually works) is not actually much more efficient than the latest iterations of iPS; however, media representations of such counterpoints have been scarce. Additionally, it is well known that papers in Nature (and other journals) are more than occasionally thought-provoking but not reproducible, but the media painted this preliminary study as something ironclad that had already changed the field; a writer from the Asahi Shimbun even told a friend of mine “if it is published by Nature, you would believe it.” The STAP concept is interesting, but the media exaggeration prematurely built STAP into something that it was not, resulting in a public perception that STAP was some kind of all-powerful messiah of regenerative medicine, which has given it a higher height to fall down from. It is therefore heartening to see the more balanced reporting you have described above, although I do believe that the coverage from the LA Times and the Boston Globe has been pretty good throughout. I hope that other media outlets (especially those in Japan) can learn from them and actually take the time to do a little bit of background investigation before writing to increase their accuracy, for the sake of the field.

joe garai评论

Dr. Lee’s result actually shows the opposite of what he claims: STAP method didn’t work again. I do not know why he was saying something as if it was a positive result. When I compare the mRNA level of parental cells and iPS, I observe THREE ORDER of MAGNITUDE, 1000-2000 fold increase of Oct4, Sox2. If you see only 7-8 fold, that’s a “noise”. Stressed cells, dying cells, damaged cells show lots of “noise”, or “error bars”. It’s funny that Dr. Lee’s result shows no error bar. In addition, he uses only one house keeping gene normalization control, which often result in skewed result. I always use 3-5 different genes to confirm the result.

asculum评论
But the cells were actually a mixture of dying and “STAP” cells so you wouldn’t expect the same increase in transcript levels that is seen in pure iPS cells.

David 评论

I suspect he thought by contributing the blog he was doing something interesting for his students, as well as addressing something well publicized in the media? However, the rather rapid gear changes he has performed indicate I suspect that he was not expecting the media pressure that comes with blogging. All of that plus the blog comments themselves I could well imagine threaten his reputation, and he thought ..what the heck!

I sense that it is the normal discourse within science to have rigorous debates when discussing controversial proposals. When blogging research commentary is added it may attract outgoing but naïve researchers to tip toe into difficult areas. However, there is a fine line between crowd and herd behaviour, so trying something new and reporting it depending on the nature of the subject, may bring a world of pain down on them, and then it seems it is better not to try anything new.

It seems there are many genuine questions about proving STAP cells, and due to the informative debate I have heard many different thoughts on how to test pluripotency. With the controversy regarding the Nature papers, it is going to be a brave person to ever think this is an area worth reinvestigating and thereby threaten their reputation and consequently their research funding.