University of Minnesota withdraws pioneering studies on stem cells and Alzheimer’s disease

Years after questions were raised about their integrity, two of the University of Minnesota’s highest-profile scientific discoveries were retracted in a week: one that offered hope about the therapeutic potential of stem cells and the other which opened a promising path towards the treatment of Alzheimer’s disease. .

These studies are more than a decade old and, in some ways, superseded by other findings in their fields. But the retractions of the June 24 Alzheimer’s paper and the June 17 stem cell paper are setbacks for an institution struggling to move up the U.S. rankings in terms of academic reputation and federal funding for research.

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

This shows the harm caused by the drawn-out academic investigation and the journal’s retractions, said Dr. Matthew Schrag, a neurologist who reviewed the 2022 Alzheimer’s paper outside of his role at the University. Vanderbilt. “We are wasting not only resources, but also the credibility and reputation of our profession by failing to respond to obvious misconduct. »

The university said it had numerous training and ethics requirements that were not in place at the time these articles were published and that should prevent future conflicts over the images, subject matter of the questions in both studies, and the resulting retractions.

These discoveries were remarkable at the time because they offered unexpected solutions to thorny scientific and even political problems.

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

Only stem cells from early-stage human embryos had shown such regenerative potential at that 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 embryo research, fueling the search for alternative sources of stem cells.

Dr. Karen Ashe and her colleagues also attracted worldwide attention in 2006 when they discovered a molecular target that appeared to influence the onset of Alzheimer’s disease, which remains incurable and one of the leading sources of dementia and death in the aging population of the United States.

Mice mimicking this molecule, amyloid beta star 56, showed greater memory loss due to their ability to navigate a maze. Ashe hypothesized that a drug targeting this molecule could help people overcome or slow the debilitating effects of Alzheimer’s disease.

The problems that led to the retractions were remarkably similar. Colleagues at other institutions struggled to reproduce their findings, prompting others to look more closely at the images of cellular or molecular activity in mice on which their findings were based.

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

“The claim that these were essentially embryonic stem cells and that they could differentiate into anything, no one has been able to reproduce that,” he said.

Verfaillie and his colleagues corrected the Nature In 2007, Verfaillie published a paper in which she published an image of mouse cellular activity that appeared identical to an image in another paper, which supposedly came from different mice. The University then launched an investigation into complaints about duplication or manipulation of images in other Verfaillie articles.

He ultimately cleared her of any misconduct, but blamed her for inadequate training and oversight and claimed that a younger researcher had falsified data from a similar study published in the journal. Blood. This article was retired in 2009.

Concerns resurfaced in 2019 about the Nature stem cell article when Elisabeth Bik, a microbiologist turned research detective, found other examples of image duplication.

Bik has also emerged as a key critic of Ashe’s findings on Alzheimer’s disease, raising concerns about the images it contains. Nature article and several related studies. So far, much of the blame falls on co-author Sylvain Lesne, a neuroscientist at the University who is responsible for the published images. Lesne did not respond to a request for comment, but allowed the university to disclose that it had completed its internal investigation into the matter. Nature paper without finding any evidence of misconduct. Analyzes of other publications from Lesne’s laboratory are underway.

Changes over the past decade at the university have sought to reduce academic scandals, including the addition of a system in 2008 for anonymous reporting and handling accusations. All researchers conducting studies at the University must complete required training which advises them on how to avoid conflicts of interest, plagiarism and professional misconduct.

Although the articles continue to be cited, researchers have turned their attention to other targets. Ashe turned his attention to finding a drug that could stop dysfunctional tau proteins from disrupting the brain’s thinking cells, or neurons.

Ashe said she agreed with Nature reluctantly retracted, because she published follow-up research that offered new evidence for her findings and recommended a correction. Nature document which would have further confirmed these conclusions.

“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 on Abeta *56 and continue to believe that it could improve our understanding of Alzheimer’s disease and the development of better treatments.

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

Verfaillie headed the university’s stem cell institute and remained involved in its research even after returning to Belgium in 2006. The recent retiree did not respond to an email for comment, but said in a translation from a Belgian newspaper article that the retraction is “a stain on our reputation.” Nature requested the correction because Verfaillie and other authors were unable to locate authentic images to prove the validity of their research.

“There is indeed a problem with a photo,” she said. “We haven’t found the right photo twenty years after the search was carried out. But even without this photo, the conclusion still stands.”

The debate over the usefulness of mesenchymal stem cells became less prominent in 2007, when Shinya Yamanaka revealed 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, earning the Japanese researcher a share of the 2012 Nobel Prize in Medicine.

Aldhous said it was disappointing that it took four years to resolve questions related to the Alzheimer’s article, and much longer to do the same regarding the stem cell article. He said he didn’t think the university adequately addressed whether researchers made repeated errors or engaged in intentional misconduct. The junior researcher accused of errors in a stem cell paper was not a listed author on other controversial papers, he noted.

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

“Why did we have to wait so long to throw this in the trash, basically?” He asked. “This should have happened years ago.”

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