31 studies on cardiac stem cells from Harvard lab retracted

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Harvard Medical School and Brigham and Women’s Hospital have recommended that 31 papers from a former lab director be retracted from medical journals. Stat News reports that the two institutions said the papers from the lab of Dr Piero Anversa, who studied cardiac stem cells, “included falsified and/or fabricated data.”

Last year, the hospital agreed to a $10m settlement with the US government over allegations Anversa and two colleagues’ work had been used to fraudulently obtain federal funding. Anversa and Dr Annarosa Leri – who have had at least one paper already retracted, and one subject to an expression of concern – had at one point sued Harvard and the Brigham unsuccessfully for alerting journals to problems in their work back in 2014. Anversa’s lab closed in 2015; Anversa, Leri, and their colleague Dr Jan Kajstura no longer work at the hospital.

While the Brigham settled with the US Department of Justice, the US Office of Research Integrity, which oversees research misconduct investigations involving National Institutes of Health funding, has not made a finding in the case.

The report says the university and the hospital have not said which journals the 31 papers appeared in, but the journal Circulation retracted a paper by Anversa and colleagues in 2014, and The Lancet issued an expression of concern about another in the same year. It is not clear how, or whether, the call for retractions by Harvard and the Brigham is related to the Brigham’s settlement with the government.

“Following a review of research conducted in the former lab of Piero Anversa, we determined that 31 publications included falsified and/or fabricated data, and we have notified all relevant journals,” Harvard and the Brigham are quoted in the report as saying. Anversa has previously corrected eight of his papers, many for failures to disclose conflicts of interest.

The report says Anversa’s work was based on the idea that the heart contains stem cells that could regenerate cardiac muscle. He and his colleagues claimed that they had identified such cells, known as c-kit cells. When various research teams tried to reproduce the results, however, they failed. Still, some scientists have tried to inject c-kit cells into damaged hearts, with mixed results at best.

“For ten years, he ran everything,” said Jeffery Molkentin, a researcher at Cincinnati Children’s Hospital whose lab was among the first to question the basis of Anversa’s results in a 2014 paper in Nature. “It really is a relief that this has been corrected. I think this is good for everybody.”

For the most part, “the field has already worked this in,” Molkentin said in the report. “It’s like when Wall Street has worked in the next two interest rate hikes.” Still, he said, a small number of researchers continue to publish findings that agree with Anversa’s. “Maybe these 31 retractions will keep pushing the pendulum a little further to the right and these people will slowly start to back off even more,” he said. “It’s just discouraging when you see these papers keep popping up,” Molkentin said. “There are no stem cells in the heart. Quit trying to publish those results.”

The report says Anversa published at least 55 papers that listed Harvard as an affiliation. In 2014, a former research fellow described an atmosphere of fear and information control in his lab.

Anversa, who according to publications was most recently affiliated with the Cardiocentro Ticino and University of Zurich, could not be reached for comment. The report says an email to his address at Cardiocentro Ticino bounced back. A number of Anversa’s co-authors either did not immediately respond to a request for comment, or declined.

“We are committed to upholding the highest ethical standards and to rigorously maintaining the integrity of our research,” Harvard and the Brigham said. “Any concerns brought to our attention are reviewed in accordance with institutional policies and applicable regulations.”

Anversa was born in Parma, Italy, in 1940 and received his medical degree from the University of Parma in 1965. The report says he gained prominence as a stem-cell researcher at New York Medical College in Valhalla, New York, where he worked before moving to Harvard Medical School and the Brigham in 2007. Anversa became a full professor in 2010.

Throughout his career, Anversa has received several commendations, including a research achievement award from the American Heart Association, which in 2004 also named him a “distinguished scientist.”

The report says although journals often act on retraction recommendations by universities, they do not always do so, and it sometimes takes a while. Journals retract roughly 1,400 scholarly papers each year, out of some 3m total publications. Anversa’s total would put him in the top 20 list of scientists with the most retractions in the world.

The 10 scientists worldwide with the most retracted papers have at least 39, and in one case – Japanese anesthesiologist Yoshitaka Fujii – 183 such articles.

So, what do the calls for retraction mean for cardiology? “What seems obvious to me is a need for transparency,” Yale cardiologist Dr Harlan Krumholz is quoted in the report as saying. “The scientific community needs to know what was found, why papers were retracted, and what is recommended with regard to his work going forward. Also, what has happened to work that was based on his work. Without this knowledge it is hard to know what it means.”

Stat News report

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