University of Minnesota withdraws groundbreaking research on stem cells and Alzheimer’s disease

Years after questions were raised about their integrity, two of the University of Minnesota’s most prominent scientific discoveries have been retracted in the space of one week: one that offered hope for the therapeutic potential of stem cells and the other that offered a promising path to treating Alzheimer’s disease.

The studies are more than a decade old and in some ways have been superseded by other discoveries in their field. But the retractions of the June 24 Alzheimer’s article and the June 17 stem cell article are setbacks for an institution that has been fighting to move up the U.S. rankings in academic reputation and federal research dollars.

Both studies have been published in Nature and have been cited nearly 7,000 times in other papers, studies and articles. Researchers around the world were with the help of these papers to support their work years after they were challenged.

That shows the damage of the journal’s lengthy university research and retractions, said Dr. Matthew Schrag, a neurologist who reviewed the Alzheimer’s paper in 2022 outside his role at Vanderbilt University. “We are wasting not only resources but also the credibility and reputation of our profession by failing to address clear misconduct.”

The university said there are many training and ethics requirements that did not exist when these articles were published. These requirements should prevent future disputes over images, the focus of the questions in both studies, and resulting retractions.

The discoveries were remarkable in their time because they offered unexpected solutions to difficult scientific and even political problems.

Dr. Catherine Verfaillie and colleagues reported in 2002 that they were able to coax mesenchymal stem cells from the bone marrow of adults to grow numerous other cell types and tissues in the body.

Only stem cells from early-stage human embryos showed such regenerative potential at the time, and they were controversial because they came from aborted fetuses or leftover embryos from infertility treatments. President George W. Bush had banned federal funding for embryonic research, fueling the search for alternative stem cell sources.

Dr. Karen Ashe and colleagues also gained global attention in 2006 when they found a molecular target that appeared influential in the pathogenesis of Alzheimer’s disease, which remains incurable and a leading source of dementia and death in the aging US population.

Mice that mimicked that molecule, amyloid beta star 56, showed more severe memory loss based on their ability to navigate a maze. Ashe theorized that a drug that targets that molecule could help people overcome or slow the debilitating effects of Alzheimer’s.

The issues that led to the withdrawals were remarkably similar. Colleagues at other institutions struggled to replicate their findings, prompting others to take a closer look at the images of cellular or molecular activity in mice on which their findings were based.

Peter Aldhous first raised concerns about the discovery of stem cells in 2006 as a science journalist and San Francisco bureau chief for New scientist magazine.

“The grand claim that these were essentially the same as embryonic stem cells and could differentiate into anything, no one could replicate,” he said.

Verfaillie and colleagues corrected it Nature article from 2007, which contained an image of cellular activity in mice that appeared identical to an image in another article purportedly from different mice. The U subsequently launched an investigation into complaints about duplications or manipulations of images in more of Verfaillie’s papers.

It ultimately cleared her of misconduct, but accused her of inadequate training and supervision and alleged that a junior researcher falsified data in a similar study published in the journal Blood. That article was retracted in 2009.

In 2019, concerns about Nature’s stem cell article resurfaced when Elisabeth Bik, a microbiologist turned investigative detective, found more examples of image duplication.

Bik also proved to be a major critic of Ashe’s discoveries about Alzheimer’s disease, raising concerns about the images in her Nature paper and several related studies. Much of the blame so far lies with co-author Sylvain Lesne, an American neuroscientist responsible for the published images. Lesne did not respond to a request for comment, but allowed the university to announce that it had completed its internal investigation into the matter Nature without finding any evidence of wrongdoing. Reviews of other publications from Lesne’s lab are ongoing.

Changes over the past decade at the university have sought to reduce academic scandals, including a system added in 2008 for anonymous reporting and allegations management. All researchers leading studies at the U must complete required training that advises them on avoiding conflicts of interest, plagiarism and misconduct.

Even as the articles continue to be cited, researchers have turned to other targets. Ashe has focused on the search for a drug that can prevent dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.

Ashe said she agreed to the Nature she reluctantly retracted, having published follow-up research that provided new evidence of her findings and recommended a correction of the findings Nature article that would have further confirmed these findings.

“However, when the editors decided not to publish the correction, I chose to retract the article,” she said in an email, adding that “we are encouraged by the results of ongoing experiments with Abeta*56, and continue to believe that this could be possible. improve our understanding of Alzheimer’s disease and the development of better treatments.”

Lesne was the only co-author to disagree with the retraction, despite Nature stating that the paper contained “excessive manipulation, including splicing, duplication and the use of an eraser” to edit the images.

Verfaillie headed the university’s stem cell institute and remained involved in the research even after his return to Belgium in 2006. The recently retired did not respond to an email seeking comment, but said in a translation of a Belgian newspaper article that the retraction “is a stain on our reputation.” Nature called for the correction because Verfaillie and other authors could not find authentic images to prove the validity of their research.

“There is indeed a problem with a photo,” she said. “Twenty years after the research, we have not yet found the right photo. But even without that photo, the conclusion still stands.”

The dispute over the usefulness of mesenchymal stem cells became less significant in 2007, when Shinya Yamanaka unveiled a process for reprogramming mouse skin cells so that they could mimic the versatility of embryonic stem cells. Others were able to repeat the process, which earned the Japanese researcher a share of the 2012 Nobel Prize in Medicine.

Aldhous said it’s disappointing that it took four years to resolve questions about the Alzheimer’s article, and much longer to do the same about the stem cell article. He said he does not believe the university has adequately resolved whether the investigators made repeated mistakes or committed intentional misconduct. The junior researcher blamed for errors in a stem cell paper was not a listed author on other disputed papers, he noted.

However, he said it is arguably more important to correct the science quickly so that flawed or unsubstantiated research does not influence other scientists and send them in the wrong direction.

“Why did we have to wait so long to actually throw this in the trash?” he asked. “This should have been done years ago.”

StarTribune 2024. Distributed by Tribune Content Agency, LLC.