Readers of Nature, one of the world’s most important scientific journals, might have been struck recently by an audacious claim appearing on its website about a possible stem cell treatment for heart attacks.

The published item asserted that MUSE cells, a subset of stem cells, could regenerate heart tissue after acute myocardial infarctions, which are deadly sudden heart attacks. This could be a significant advance in both cardiac treatment and the use of stem cells.

Here’s the problem. The published item wasn’t a peer-reviewed article subject to Nature’s rigorous professional vetting procedure. It was an advertisement placed by the Translational Research Center for Medical Innovation, the Japanese research lab that says it performed the reported study on MUSE cells using white rabbits.

The field of science doesn’t need to blur the line between research articles and ads. UC Davis stem cell expert Paul Knoepfler


It looked like a Nature article, however, at least to Paul Knoepfler, a stem cell expert at UC Davis who has become one of our most assiduous debunkers of stem-cell quackery. Knoepfler thought the layout of the item might cause some readers to mistake it for a peer-reviewed paper, and promptly queried Nature. The journal responded by taking the advertisement offline Feb. 22. Knoepfler’s brief chronicle of the affair can be found on his website here.

Nature’s defense is that the item was “clearly marked as an advertisement feature and included a disclaimer beneath to explain that it had not been subject to peer review,” a spokesperson for Springer Nature, the journal’s publisher, told me by email. But the journal also acknowledged that the “advertisement was made available on Nature Research’s website before it had been through all our internal approvals.”

Advertising, or the real thing? A stem cell researcher thought this ad in Nature could be mistaken for a peer-reviewed article. Nature removed the ad. (Nature, via P. Knoepfler)

After Knoepfler’s inquiry, the journal said, “we reviewed the ad and determined that it didn’t fully meet the guidelines we set ourselves for paid content” and removed it. Nature told Knoepfler that such advertising material wasn’t subject to indexing for scholarly databases and therefore wouldn’t penetrate the research mainstream.


It’s proper to observe that Nature was doing something that has come naturally to many publications, including The Times—running “native advertising” designed to replicate the form and layout of the legitimate editorial material that surrounds it. Nature says in its defense that “like most commercial publishers, we generate revenue by allowing advertisers access to our different audiences. That revenue, in turn, allows us to produce even more great content.”

Still, the drawbacks of mixing paid- and proper material on a website as influential as Nature’s should be obvious.

“How can a research article be an advertisement?” Knoepfler asked on his blog. “I don’t think it should be possible. The field of science doesn’t need to blur the line between research articles and ads.”

The dangers are especially great when the topic lends itself to confusion and exploitation by unscrupulous healthcare promoters. The stem cell field matches that description to a T, since promoters of unproven treatments have used the public’s impression of stem cells as the source of miracle cures to relieve thousands of desperate patients of tens of thousands of dollars at a clip. Any stem cell-related material offered for publication, whether as peer-reviewable research or paid content, therefore, needs to be vetted with special care.


It’s true, as Nature asserts, that the MUSE ad was bookended on its website with a heading identifying it as an “advertising feature” and a disclaimer that it “has not been peer reviewed” and that “the advertiser retains sole responsibility for its content.”

A link on the article directed users to a page explaining Nature’s policies on paid content. The MUSE ad fell into the category of “advertisement content,” some of which advertisers could “commission Nature Research Custom Media, a division separate from other editorial departments, to create relevant content on their behalf…. Advertisers have ultimate approval over paid content.”

That sounds like an acknowledgement that Nature retained some control over the visual appearance, at least, of advertising content — which underscores the questions over why it allowed an ad to mimic the layout and style of a peer-reviewed research paper. Knoepfler observes that the top heading of the webpage on which the ad appeared bore the legend “nature>article,” which could create more confusion over the source and reliability of the subsequent material.

That brings us to the issue of MUSE cells themselves. The acronym derives from “multilineage-differentiating stress-enduring” cells. These were first identified in 2010 by Japanese researchers, who reported finding them in bone marrow and skin tissue. The researchers said MUSE cells are activated by stress such as cold temperature, starvation or oxygen deprivation, at which point they exhibit markers of pluripotency, meaning they can be made to replicate different cell types in the body — a Holy Grail for stem cell scientists.


Questions persist over whether MUSE cells are for real or whether they can fulfill their discoverers’ ambitions for them. They have supporters and skeptics. Among the former are researchers at UCLA, who also found them in adipose, or fat, tissue. Among the virtues of MUSE cells, it’s said, is that they’re less likely than other forms of stem cells to produce tumors when they’re transplanted.

Others, including Alexey Bersenev of Yale, have expressed more doubt. Knoepfler, for his part, writes that the MUSE boomlet is worrisomely reminiscent of earlier claims for stem cell variants that ended up getting debunked after creating frenzies of enthusiasm.

Watch out for claims about adipose-derived MUSE cells becoming part of the arsenal of questionable stem-cell clinics hawking expensive, unproven treatments for a host of diseases — multiple sclerosis, Parkinson’s, diabetes, etc., etc. — using fat cells drawn from the body by liposuction and then reinjected stem cell extraction.

The Food and Drug Administration has its hands full monitoring these claims and treatments. The agency has issued multiple warnings to steer the public away from such clinics and has taken administrative and legal action against some of them. The signs point to more exploitation and more danger to the public health. Important journals such as Nature shouldn’t be participating in a race to the bottom.


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