Much-cited Nature stem cell paper retracted after 22 years

A 2002 Nature paper claiming that adult stem cells from bone marrow can become nearly any cell type has been retracted by Nature, making it the most-cited retracted paper ever.

The paper was published under Professor Catherine Verfaillie's supervision, who at the time led the Stem Cell Institute at the University of Minnesota. The results claimed that a type of adult stem cell extracted from bone marrow, called multipotent adult progenitor cells (MAPCs), could, under certain circumstances, contribute to all the major cell types of the body, including brain, heart, skin, blood and lung.

'… the Editors no longer have confidence that the conclusion that MAPCs engraft in the bone marrow is supported… the Editors no longer have confidence in the reliability of the data reported in this article,' Nature concluded.

The discovery in 2002 generated excitement because no other adult stem cells had shown such potential, similar to embryonic stem cells. More so, the findings supported the claim that MAPCs 'engraft' in the bone marrow. In other words, they successfully settle and integrate into the bone marrow, which is the body's factory for producing blood cells. Once engrafted, these adult stem cells can start generating new, healthy blood cells, potentially helping treat diseases affecting blood and the immune system, such as leukaemia.

The paper was cited almost 4500 times, forming the basis for numerous studies and a Nobel Prize, according to the Belgian newspaper De Morgen. However, replication issues and concerns about image manipulation emerged over the years.

In 2007, the magazine New Scientist questioned the data in Professor Verfaillie's 2002 Nature paper, resulting in corrections published in Nature that, according to the authors, 'do not alter the conclusions of the article'.

Later that year, a part of the results was reproduced by Professor Irving Weissman's group at Stanford University and published in the Journal of Experimental Medicine (see BioNews 393).

In 2019, Dutch microbiologist Dr Elisabeth Bik, an image integrity expert who sparked numerous science paper retractions, identified issues with several images in the Nature paper, noting that two bone marrow images were too similar to represent different samples and another liver tissue image showed signs of Photoshop manipulation.

Since the researchers could not provide the original lab photos to clarify the situation, Nature decided to retract the paper completely. Despite that most authors agreed with the retraction, Professor Verfaillie still finds the retraction unjustified.

'It's a stain on my reputation, I've lost several nights of sleep over it,' commented Professor Verfaillie to De Standaard, now an emeritus professor at the Catholic University of Leuven (KU Leuven) in Belgium. 'There is an issue with a bone marrow photo. We couldn't find the correct photo twenty years after the research. But even without it, the study's conclusions remain valid'.

Professor Verfaillie continued: 'For the liver tissue image, we're unsure what went wrong. We located the original photo, with no issues, and provided it to Nature, but they claim we can't prove its authenticity.'

According to Retraction Watch, a specialised site that tracks issues in the scientific community, this is the fourth retraction for Professor Verfaillie, including a 2001 precursor article published in the journal Blood, which was eventually retracted in 2009 due to falsified images. Professor Verfaillie was cleared of academic misconduct by the University of Minnesota but criticised for insufficient oversight. A 2019 investigation by KU Leuven confirmed issues with Professor Verfaillie's articles but found 'no breach of research integrity' by her or her lab's researchers.

It remains unclear why Nature took so long to retract the 2002 paper.