Acid-bath method for making stem cells under fire

A surprisingly simple method for creating stem cells by dipping cells in acid has so far proven impossible to replicate, prompting calls for the original research papers, published in January, to be retracted. One of those calls is coming from inside the large group of collaborators that first introduced the STAP stem cells, a special kind of ultraflexible cell shown to produce any type of cell in the body and some in the placenta (SN: 2/22/14, p. 6).

Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, and colleagues first reported in two January 29 papers in Nature that they had reprogrammed newborn mouse cells by dunking them into acid or squeezing them. The cells took on stem cell–like qualities and were dubbed STAP cells for stimulus-triggered acquisition of pluripotency. So far, no other researchers have been able to repeat the accomplishment.

Qi-Long Ying, a stem cell biologist at the University of Southern California Keck School of Medicine in Los Angeles, has tried twice to make STAP cells without success. He is not alone. Ten reported attempts posted to a blog maintained by stem cell researcher Paul Knoepfler of the University of California, Davis have also failed.

“No one has told me privately they could get it to work,” Knoepfler says. “If anyone is getting it to work, they’re really keeping a tight lid on it. Of course, we can’t know what people aren’t telling us.”

On March 5, Obokata and colleagues Yoshiki Sasai and Hitoshi Niwa released detailed tips for replicating the procedure for making the cells.

It’s clear from the tutorial that the technique is not as straightforward as it was originally portrayed. “This is not an easy method,” Knoepfler says. “That doesn’t mean it’s wrong; it just may be something one can only rarely get to work.”

But the papers have also come under scrutiny because of allegations of plagiarism and image duplication. “Crucial mistakes” in the research led one of the original study coauthors, Teruhiko Wakayama of Yamanashi University in Japan, to ask Obokata to retract the papers from publication, the Wall Street Journal reported on March 10. Nature and RIKEN have launched independent investigations.

“I think it is still too early to call for a retraction of the STAP papers,” Ying said in an e-mail. “Nature should invite Dr. Haruko Obokata to replicate her own STAP results in an independent and reputable lab chosen by Nature. This is the most efficient way to prove whether the STAP story is true or not.”

Other researchers say that the onus is on the authors to show the validity of the work. But with dissension within the original research team, “it’s not going to be a smooth road to clarity,” Knoepfler says.