Questions linger over stress-induced stem cells

Kiyoshi Ota/Bloomberg via Getty

Problems with stem-cell papers noted at a RIKEN conference in March 2014 have now been further analysed.

The latest investigation into a debunked method of generating stem cells has left researchers grappling with questions about what went wrong in a laboratory at the RIKEN research institute in Japan.

The final report from the independent investigation, released on 26 December, bolstered suspicions that the stem cells which were supposedly generated by applying stress to ordinary adult cells in an acid bath were actually embryonic stem cells that had been introduced to the samples. But investigators were unable to determine how the contamination occurred or whether it was accidental.

The investigation also has not explained one of the most notable features of the cells their ability to form a placenta something that embryonic stem cells do not generally do. That is still one question that to me is still a mystery, says Manuel Serrano, a cancer biologist who has worked with stem cells at the Spanish National Cancer Research Centre in Madrid.

Serrano, like many of his colleagues, was intrigued by the papers, published in Nature in January 2014, reporting that adult cells could behave like stem cells after experiencing severe stress1, 2. To him, the premise made sense there was ample evidence in the literature that stressed cells were prone to taking on new identities. Cells respond to damage by trying to acquire the plasticity to repair the tissue, he says. But it was surprising that this stress was sufficient to fully reprogram the cell.

Serrano tasked two researchers in his lab with making stem cells using the authors method called stimulus-triggered acquisition of pluripotency (STAP). He initially urged them to keep trying when their attempts failed. But within about two months, Serrano advised them to abandon their efforts. Reports were pouring in from other labs that could not reproduce the method, and questions arose about the validity of data in the papers.

In response to the controversy, RIKEN launched two investigations into the work, much of which was carried out at the RIKEN Center for Developmental Biology in Kobe. An internal review reported in March that lead investigator Haruko Obokata had manipulated images in the two Nature publications. The papers were retracted in July3.

The second investigation, carried out by a team of scientists not employed by RIKEN, delved deeper, analysing cell lines and tissue samples from the laboratories to determine their provenance. In addition to unearthing two more fabrications in figures from the January publications, the team found that three STAP cell lines contained embryonic stem cells.

The results confirmed suspicions in the field, says George Daley, a stem-cell researcher at Childrens Hospital Boston in Massachusetts. The fact that the reported STAP cells had different properties from embryonic stem cells was what piqued many peoples interest, he says. But there was always the concern that some part of the data could have come from the use of standard embryonic stem-cell lines.

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Questions linger over stress-induced stem cells