Report challenges blood stem cell role in rebuilding heart

One of the most spectacular biomedical findings of the past few years was called into question yesterday when scientists published evidence that they had failed to get stem cells in the blood to rebuild the heart.

The work, reported in the prestigious journal Nature, appears to undermine a landmark 2001 study that gave many doctors and patients hope that medicine could overcome one of the nation's leading killers by finding a way to repair damaged heart tissue.

The new report is also politically charged, since it undercuts a key premise of the Bush administration's limits on embryonic stem cell research. The Bush policy was built partly in the belief that adult stem cells, such as those used in the study, are almost as flexible as the more controversial embryonic cells. But the new findings are part of a wave of new, more rigorous research showing that many of those early claims for adult stem cells were wrong.

"These papers are both very definitive, and they represent very contrary information to earlier data," said Dr. George Q. Daley, a leading specialist in blood stem cells at Children's Hospital in Boston.

The new studies aimed to replicate and expand on the 2001 experiment, which caused a sensation among biologists, cardiologists, and desperate patients. The original experiment seemed to show that cells taken from the bone marrow of an adult mouse could rebuild heart tissue. For biologists, it suggested that adult stem cells from blood might be more flexible than some researchers had believed, able to transform from blood to heart muscle and perhaps other types of tissue.

But the new experiments, conducted by two separate teams of scientists and published online, re-created the original research and used a variety of methods to track the blood stem cells. The scientists found that none of the cells turned into heart tissue. The authors argue that the original results were based on unfounded leaps of interpretation.

The controversy, which has now moved from arguments at scientific conferences to the pages of a top journal, has broad implications. Finding a way to heal hearts could bring tremendous medical benefits and financial rewards, and a number of human clinical trials, including one in Boston, are based on the idea that blood cells could do the job. One of the papers published yesterday explicitly charges that the trials are "premature."

The findings do not mean that cells taken from the blood or bone marrow cannot help patients with damaged hearts, scientists said. Indeed, a number of clinical trials suggest that such a technique can bring modest benefits. But the new papers argue that scientists do not understand what is causing the benefits.

The senior author of the 2001 paper, Dr. Piero Anversa of New York Medical College, dismissed the new criticism, saying the other scientists -- at Stanford University, the University of Washington, and Indiana University -- may have made subtle technical mistakes. More important, he said, the ongoing clinical trials support his finding.

"The truth will be very clear in a very short period of time," said Anversa, whose 2001 paper was also published in Nature.

Feeding the dispute is a cultural divide between those in the laboratory, who want to understand precisely how a therapy works, and those in the clinic, who want to help their patients even if the underlying science is not fully understood.

At Caritas St. Elizabeth's Medical Center in Brighton, doctors are using stem cells taken from the blood of patients to try to heal heart damage. Dr. Douglas W. Losordo, chief of cardiology, said that the papers published yesterday will not affect the trial and that the work already conducted in animals suggests it will be successful.

The goal of the new papers was not to assess the clinical trials, but to see whether the impressive biological claim that helped launch them -- that blood stem cells are building new heart tissue -- is true.

The experiments focus on a condition, called a myocardial infarction, in which a vessel that supplies blood to part of the heart is blocked, cutting off oxygen and killing the cells. In the 2001 Anversa study, researchers cut off the blood supply to part of the heart in mice, then injected them with cells taken from the bone marrow and marked with a fluorescent substance. The mice treated with the cells had healthier hearts, and an examination showed areas filled with fluorescent cells, suggesting they had rebuilt the heart.

Anversa's finding supported the idea that stem cells from the blood could change their identity depending on the environment they were placed in -- an electrifying idea, because the cells are already used by doctors for bone marrow transplants. Perhaps, some speculated at the time, the same cells could be used to rebuild tissues throughout the body.

The new experiments leave open the possibility that the cells could have a beneficial effect, but not by rebuilding tissue. The new experiments used an array of methods to track the cells, making them less prone to error than the one used in the original study, according to scientists. The lead authors of the two papers are Dr. Leora B. Balsam of the Stanford University School of Medicine and Dr. Charles E. Murry of the University of Washington.

There are several explanations for the discrepancy. One possibility is that the cell samples used by the investigators are different, said Dr. Bernardo Nadal-Ginard, a visiting professor at New York Medical College and one of the authors of the original paper. Bone marrow is filled with many types of cells, and the scientists behind the new work may have filtered out a type of cell that is capable of rebuilding the heart, even if they are not the blood stem cell they were originally thought to be.

Another possibility is that the bone marrow cells are not rebuilding the heart, but are instead releasing compounds that protect the heart cells when they are deprived of oxygen, said Dr. Victor Dzau, a cardiologist who is chairman of the department of medicine at Brigham and Women's Hospital in Boston.

Dzau said the clinical trial results are encouraging but preliminary, and the new research underlines the urgent need to understand the biology better. Only with this understanding, he said, can doctors give patients the correct cells, and, hopefully, deliver on the promise of making hearts better.

"My hope," Dzau said, "is that we don't throw the baby out with the bathwater."

Gareth Cook can be reached at cook@globe.com.