Promise of “easy” stem cells comes under investigation

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A mouse embryo injected with cells made pluripotent through stress, tagged with a fluorescent protein, from Haruko Obokata and Nature.

Creating stem cells is not easy — not technically, not biologically and not, you may have heard, ethically.

But ‘easy stem cells’ are exactly what the public was promised in January when a team at the Japanese RIKEN Center for Developmental Biology led by Haruko Obokata published two simultaneous papers in Nature detailing a remarkably simple process. A quick, thirty-minute dip in a mildly acidic solution was able to turn a variety of mouse cells, including brain, skin, lung, and liver, into stem cells. They call the process STAP: stimulus-triggered acquisition of pluripotency.

Until now, the only reliable way to create stem cells for research purposes was by using a process developed in 2006 that manipulates the genes in cells to force them into a state of induced pluripotency. This technique, called iPS, circumvented the need for human embryos and thus many of the ethical bombshells that had been plaguing stem cell research so far.

Totipotent cells are further back in the cell development process than pluripotent cells, thus they have even more potential.  Click for full size. (CREDIT: Mike Jones, Wikipedia)
Totipotent cells have even greater developmental potential than pluripotent cells. Click for full size. (CREDIT: Mike Jones, Wikipedia)

The newest technique goes a step further, circumventing the need for difficult direct genetic intervention, using adult cells, and — here’s the kicker — the stem cells created may actually be “totipotent” and not “pluripotent.” Pluripotent cells can become almost any tissue, but are notably unable to develop into placental cells. The STAP cells were able to differentiate, according to Nature, into all cell types in a developing mouse embryo — including placenta.

The final volley of incredible news came in a follow-up with New Scientist, published earlier this month wherein one of the authors of the two papers, Charles Vacanti at Harvard Medical School, provided images of what he claimed were the first successful STAP cell experiments using human tissue.

A Broken Promise?

In the words of Carl Sagan, “extraordinary claims require extraordinary evidence.” Or, in this case, at least evidence free of any questionable elements. Unfortunately, Nature news announced this week that the RIKEN institute was launching an investigation into the two high-profile STAP papers after several science blogs pointed out anomalies in the images included in the papers and in an earlier 2011 paper by the same team.

Vacanti told Nature news that he believes the image problems, at least in the 2011 paper, appear to be an honest mistake and had no effect on the methods or conclusions of the paper in question. He’s already asked for a correction from the journal that originally published the paper.

The results of RIKEN’s investigation into issues with the images in the two recent papers are forthcoming, although a RIKEN spokesperson told the Boston Globe via email that “RIKEN believes that the research results are valid.”

Meanwhile, efforts to replicate the “easy” process pioneered by Obokata’s team have not met with success, which has only heightened the uneasy skepticism now surrounding the papers.

Simple in principle, the actual protocol used by Obokata’s team may be more difficult than the press or the scientific community anticipated in their early reactions.

In Nature’s report on the investigation, Teruhiko Wakayama, cloning specialist and co-author of both recent papers, explained that while he was able to successfully reproduce the results on his own — with coaching from Obokata — he has since had difficulty reproducing the results after moving to a new lab.

Phys.org is reporting that “all [the researchers who have attempted replication] have acknowledged publicly that they have not used the same types of cells … and that the procedure … [is] actually very difficult to carry out.”

Wait and See

None of the many reports on this developing controversy has yet featured comment from Obokata herself; even the Nature news team was unable to reach her. Nature mentions hearsay that a detailed protocol will be published soon. If the issues with replication can be cleared up it may go a long way toward restoring the excitement and enthusiasm that first greeted this study.

“If they can do this in human cells, it changes everything,” Rob Lanza of Advanced Cell Technologies in Massachusetts told New Scientist, commenting on Vacanti’s preliminary success with human STAP cells.

That statement is as true as ever, but the “if” seems much bigger today than it did a few weeks ago.

The Genetic Literacy Project’s Gene-ius section will be following this story with cautious optimism.

Kenrick Vezina is the Gene-ius editor for the Genetic Literacy Project and a freelance science writer, educator, and amateur naturalist based in the Greater Boston Area.

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