Stress-Induced Stem Cell Method Questioned

HARUKO OBOKATAWhen a team led by investigators at the RIKEN Center for Developmental Biology in Kobe, Japan, reported a new method to reprogram stem cells using an external stressor, such as an acid bath or a mechanical squeeze, several researchers and media reports marveled at the simplicity of their approach. But anecdotal evidence from stem cell researchers trying to replicate the results of the two Nature studies published last month (January 29) indicates that reproducing stimulus-triggered acquisition of pluripotency (STAP) is anything but easy. “A lot of people have been trying [to replicate the studies’ results], but I have not heard any positive results yet,” said Sheng Ding, a stem cell researcher at the Gladstone Institutes in San Francisco, who did not participate in the work and has not himself attempted to reproduce STAP. “But it’s early. It has only been a few weeks.” Researchers who have tried to follow the published protocol have reported trouble with the method. “The groups that published these papers spent years and years trying to get this to work, in various forms and with different cells, so it may just be that it’s an unusual situation to actually get it to work,” said the University of California, Davis’s Paul Knoepfler, who also has not yet attempted STAP. “In some cases, the devil is in the details and sometimes, if other labs don’t have the detailed, step-by-step protocol, it can be hard to reproduce experiments.” He and others anticipate the publication of detailed STAP methods. In the three weeks since the papers were published, Knoepfler has been polling readers of his blog, asking whether they “believe” in STAP stem cells. And the responses he’s collected so far illustrate a precipitous decline in trust of the original results. Knoepfler has also been tracking stem cell researchers’ self-reported replication efforts. The scientific rigor of these efforts has varied, researchers have used different cell types, and teams could opt to share data anonymously on Knoepfler’s site. Of the 10 who have submitted to date, none have been able to replicate the original results. And 10 “prominent stem-cell scientists who responded to a questionnaire from Nature” have also indicated difficulty reproducing the results, Nature News reported, adding that one of the study’s coauthors, Teruhiko Wakayama, was himself having trouble with STAP. “If it’s really real, people should be able to replicate it,” said Ding. “Some labs, including ours, will continue to try. . . . It’s still early; we certainly need to give them the benefit of the doubt.” Haruko Obokata, lead author of both STAP studies, did not respond to The Scientist’s request for comment. Both RIKEN and Nature are following up on allegations of image duplication and manipulation posted to the website PubPeer with independent investigations of the manuscripts. But Knoepfler said he doubts these investigations will have any impact on whether—and how efficiently—other groups may be able to produce STAP stem cells. As the field awaits the release of more-detailed methods, he explained, researchers will likely focus on using induced pluripotent stem cells (iPSCs) and other trusted technologies. Still, some scientists remain curious to try the technique out for themselves. “People are going to keep trying,” said Knoepfler. “On the one hand, there’s part of me that thinks [STAP stem cells] are too good to be true,” he continued. “Maybe STAP stem cells could be real, but I think it’s not going to be easy to do. . . . I’m pretty convinced that this is not going to be an easy way to make stem cells, [but] I’d like to see a lot more data.” Update (February 20): Though he did not respond to an interview request prior to the publication of this story, study coauthor Charles Vacanti from Harvard Medical School today told The Scientist: “There has been a significant amount of interest, speculation, and scrutiny since our STAP cell papers were published in Nature [last month]. I understand that questions have been raised around certain images that were used in the publication. I believe that these concerns are a result of minor errors that occurred in the manuscript editing process and do not affect the overall content of the published reports, the scientific data, or the conclusions. Until these issues are resolved, I cannot share information beyond what has been published.”