STAP Paper Author Urges that the STAP Paper Be Withdrawn

Japanese scientist, Teruhiko Wakayama, a professor at Japan’s University of Yamanashi, who was part of the research team that described the production and characterization of STAP cells, has called for his own headline-grabbing study on stem cells to be withdrawn from publication. Wakayama says that the main findings of this paper have been thrown into doubt.

When the STAP cells came out in January it was hailed as a game-changer that could herald a new era of medical biology. The paper was published in the prestigious journal Nature and was also widely covered in Japan and across the world.

Since that time, however, there have been reports that several other scientists have been unable to replicate the Japanese team’s results. Also there seem to be some disparities with some of the paper’s data and images.

“It is no longer clear what is right,” Wakayama told public broadcaster NHK.

STAP or stress-triggered acquisition of pluripotency cells seemed to represent a simple way to reprogram mature animal cells back into an embryonic-like state that would allow them to generate many types of tissue.

From these STAP cell papers, various editorials dreamed big and suggested that just about any cell in your body could be simply and cheaply reprogrammed back into embryonic cell-like cells, and be used to replace damaged cells or grow new organs for sick and injured people.

Wakayama even said, “When conducting the experiment, I believed it was absolutely right.” However, now he is not so sure. He continued: “But now that many mistakes have emerged, I think it is best to withdraw the research paper once and, using correct data and correct pictures, to prove once again the paper is right. If it turns out to be wrong, we would need to make it clear why a thing like this happened.”

A spokesperson from the journal Nature has said that they were aware of, “issues relating to this paper,” and that an investigation was underway. However, at this point, the journal had no further comment to make.

Robin Lovell-Badge, a stem cell expert at Britain’s National Institute for Medical Research, cautioned against premature assumptions on whether the research was flawed. “I have an open mind on this,” he told Reuters. “I’m waiting to hear from several serious stem cell labs around the world on whether they have been able to reproduce the methods.”

Wakayama’s co-researcher Haruko Obokata, the first author on the STAP paper, became an instant celebrity in Japan after she spoke during a Nature media briefing to science reporters all over the world about her findings.

The Japanese team was joined by other researchers from Brigham and Women’s Hospital and Harvard Medical School in the United States in this research. They took skin and blood cells from mice, grew them, and then subjected them to stresses that brought the cells “almost to the point of death.” They exposed the cells to a variety of stresses, including trauma, low oxygen levels, and acidic environments.

One of these “stressful” situations used by these researchers was to bathe their cells in a weak acid solution for around 30 minutes. Within days, the scientists said they had found that the cells had not only survived but had also recovered by naturally reverting into a state similar to that of an embryonic stem cell.

Unfortunately, other research teams have yet been able to replicate the findings, and the RIKEN Center for Developmental Biology in Japan, where Obokata works, said last week it had “launched an independent inquiry into the content of the paper.

That inquiry will be conducted by a panel of experts from within and outside RIKEN, it said, and would be published as soon as it was concluded.

A spokesperson from the RIKEN Institute declined to comment on Wakayama’s call for the paper to be withdrawn.

Expanding Blood-Making Stem Cells for Use in Patients

John Dick is a senior scientist at the University Health Network’s McEwen Centre for Regenerative Medicine and a professor at the University of Toronto. He is also the senior investigator for a study that includes a collaboration between Canadian and Italian stem cell scientists that examined ways to expand human blood stem cells for human use.

A new master control gene was identified in this study that, when manipulated, could increase stem cell production.

In the words of Dick, “For the first time in human blood stem cells, we have established that a new class of non-coding RNA called miRNA represents a new tactic for manipulating these cells, which opens the door to expanding them for therapeutic uses.”

In 2011, Dick’s research group published a landmark paper in which he and his colleagues succeeded in isolating “CD49f+” cells. Just one of these CD49f+ cells could reconstitute an entire blood-cell making system in bone marrow. It has been known for some time that the population of blood cell-making stem cells in bone marrow is rather heterogeneous, and some cells have tremendous regenerative capacities, but others shown only slight regenerative abilities. DIck’s group isolated bone marrow stem cells that could replenish the whole blood-making system of a laboratory animal (see Notta, et al., Science 333, 218-221).

Dick has also pioneered the field of cancer stem cells when his lab identified leukemia stem cells in 1994 (Lapidot T, et al., Nature. 367, 645-8.) and colon cancer cells in 2007 (O’Brien CA, et al. Nature. 445, 106-10).

The lead author of this study, Eric Lechman, recounted his laboratory work with a master control gene known as microRNA 126 or miR-126. THis small RNA normally silences the expression of many genes, and thus keeps stem cells in a quiescent, dormant state. His strategy in working with miR-126 was to introduce new binding sites into the cell for miR-126 in order to lower the concentration of free miR-126 inside the cell. To do this, he infected stem cells with a genetically engineered virus that was loaded with miR-126 binding sites. The results were remarkable.

According to Lechman, “The virus acted like a sponge and mopped up the specific miRNA in the cells. This enabled the expression of normally expressed genes to become prominent, after which we observed a long-term expansion of the blood stem cells without exhaustion or malignant transformation.”

Given the difficult many labs have has growing sufficient quantities of blood stem cells in the laboratory, this finding could completely revolutionize blood stem cell research and clinical treatments with these stem cells.

According to Dick, “We’ve shown that if you remove the miRNA you can expand the stem cells while keeping their identity intact. That’s the key to long-term stem cell expansion for use in patients.”