Federal Officials Pause Stem Cell Trials to Detect Heart Disease | Science

Following a call for the retraction of dozens of articles from a heart stem cell research laboratory at Harvard University, federal officials announced today that the suspension of a clinical trial based on research in this area. The National Heart, Lung and Blood Institute (NHLBI) in Bethesda, Maryland, said in a statement that the impending retractions "have raised concerns about the scientific basis of this trial."

The treatment seemed safe in the 90 patients studied so far, said David Goff, director of the division of cardiovascular sciences at NHLBI. Many labs have contributed to basic research in support of the study, called CONCERT-HF, he said, not just the Harvard group. However, NHLBI is pausing the review because "it's a cautious thing to do," he said.

Laboratory studies conducted by cardiologist Piero Anversa of Harvard Medical School and Brigham and Women's hospitals in Boston suggested the presence of a certain type of stem cell in the heart called the c-kit + cell that could regenerate the heart muscle. in the mouse. If this is true, the cells could form the basis of a treatment for patients with heart failure. But several laboratories have indicated that they could not replicate some of Antwerpa's studies. In 2014, Harvard and Brigham and Women's revealed that they had opened a scientific investigation into the scientific misconduct of Antwerpa's work. (Antwerpa, who lost a lawsuit claiming that the investigation had been mismanaged, no longer works at Harvard.)

The CONCERT-HF trial in patients with chronic heart failure began recruiting 144 patients 3 years ago and was scheduled to end in about a year. Patients receive one of four possible treatments: c-kit + cells derived from the patient's own cardiac tissue, a combination of c-kit + cells and mesenchymal stem cells derived from the patient's bone marrow, stem cells mesenchymal alone or placebo. The trial recruited 125 of the 144 expected participants, Goff said. Of these, 117 had blood stem cells and cardiac tissue collected and 90 received treatment. No treatment-related safety issues occurred, although one patient died as a result of a cardiac biopsy. The Washington Post reported.

According to Mr Goff, when the CONCERT-HF trial was approved, the examiners were aware of the concerns raised by Antwerpa's work. But eight other labs had published 11 studies supporting c-kit + cell therapy. "The scientific base is really based on this independent corpus," he said. But Harvard and Brigham and Women's recommended the retraction of 31 items from the Anversa laboratory because they contained falsified or manufactured data. (At least one newspaper has already begun to remove documents.) This prompted NHLBI to convene the Data and Safety Monitoring Board, which oversees the CONCERT-HF trial. He recommended last Thursday that the trial marks a pause.

NHLBI has now suspended the trial and asked for a list of Harvard's 31 articles to make sure the lawsuit is scientifically sound "for the sake of prudence," Goff said.

He could not say how long the examination would last, but he was assured that it would be done "quickly", especially because the patients donated tissue and wait for treatment. About half of patients with chronic heart failure die within 5 years, he noted.

A long-time critic of Antwerpa's work suggested that questions about how c-kit + cells could repair heart tissue in mice suggest that the CONCERT-HF trial should never have started. "The problem is that if you do not know how something works, you do not really have a map of what needs to be improved to make it better," says Deepak Srivastava, a pediatric cardiologist and president of the Gladstone Institutes. San Francisco, California.

But other researchers believe that the trial should be completed because other basic work supports this approach. "There are many reasons to believe that there are still promises," says cardiologist Christopher Granger of Duke University in Durham, North Carolina, experienced in clinical trials.

And cardiologist Roberto Bolli of the University of Louisville, Kentucky, long-time collaborator of Antwerpa and co-principal investigator (co-PI) of the CONCERT-HF trial, says that even though Antwerpa argues that c-kit + cells get grafted into the heart and differentiate heart cells have been "debunked", other work supports the idea that these cells help by secreting so-called paracrine factors that promote growth of heart tissue. "Controversy [over Anversa’s work] does not really change the validity of using c-kit cells, "says Bolli.

Another trial, based in Florida, planned to start treating infants born with some cardiac malformation with c-kit + cells this month; Principal Investigator Joshua Hare from the University of Miami, Florida, did not respond to a request for comment.

Goff said NHLBI continues to support basic research on c-kit + cells and heart disease – he is now funding eight preclinical grants, he said.

With reportage Jennifer Couzin-Frankel.