Stem-cell furore erupts

Data analysis ignites public row.

Thomas Skutella.

Long-rumbling hostilities between stem-cell researchers in Germany exploded into a blazing public row last week, after Nature published a critical reanalysis of data from a high-profile 2008 article.

The researchers behind the original work¹, led by Thomas Skutella of the University of Tübingen, reported using cells from adult human testes to create pluripotent stem cells with similar properties to embryonic stem cells.

Unlike other adult cells, these reproductive or 'germline' stem cells can be reprogrammed for pluripotency without the need to introduce additional genes, a step that often relies on a virus. That could make them safer for future use in medicine.

The paper made headlines because such pluripotent stem cells might be used instead of ethically sensitive human embryonic tissue. Soon after its publication, however, some stem-cell scientists said that the evidence for pluripotency was unconvincing. They also complained that Skutella would not distribute cells to other labs for verification, even though Nature requires its authors to share all published research resources.

Hans Schöler, a director at the Max Planck Institute for Molecular Biomedicine in Münster and an author of last week's critical comment², says that he proclaimed Skutella's achievement as a breakthrough when he first saw the data at a meeting, but became doubtful after seeing the published paper. "If this paper is wrong, then a lot of scientists are wasting time, energy and money in trying to follow up on it," he says. Others fear that the episode is undermining the credibility of the field.

In response, Skutella last week asked the DFG, Germany's main research-funding agency, to conduct an investigation both of his paper in Nature and of what he claims is a witch-hunt against him. Schöler, who also works with germline stem cells, says that he would welcome such a move.

Pluripotent cells should form teratomas — encapsulated tumours comprising different cell types — when injected under the skin of mice, and also exhibit a particular profile of gene expression. "The teratoma pictures in the Nature paper were not terribly convincing but that didn't concern me too much at first," says Schöler. "It was the failure to provide cells that started to concern me." After more than a year of requests for access, he decided to reanalyse data in the paper in Nature showing which genes in the disputed cells were being expressed.

Together with bioinformaticians, he compared the genes' expression profile with those of other cells in public databases and found that it overlapped with a type of connective-tissue cell called fibroblasts but not with pluripotent stem cells. Schöler suggests that fibroblasts may have contaminated Skutella's samples. But Skutella and his colleagues deny³ mistaking fibroblasts for pluripotent cells. Skutella says that comparison of gene-expression data is meaningless "if the cells being compared were not processed identically".

Takashi Shinohara at Kyoto University in Japan, whose team in 2004 generated the first pluripotent germline stem cells from mice, shares Schöler's concerns about the expression data. He says that fibroblasts and pluripotent cells have different gene-expression profiles even if the cells are not processed in similar ways, and adds that it would be helpful to see Skutella's cells.

In a corrigendum to his original paper in August 2009, Skutella and his co-authors said that they wanted to share the cells but that the original agreement signed by tissue donors precluded distribution to third parties. Having gained broader consent from some donors, Skutella now promises to distribute the cells once they have been quality-checked. But stem-cell researcher Rudolf Jaenisch at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, is not impressed: "It's a big problem not providing the cells for what is nearly two years — whatever the excuses, this is bad."

Ulrike Beisiegel, ombudsman for the DFG, says her office will decide "soon" whether to take up the investigations.