June 7, 2001 - Study Finds Heart Regenerates Cells
By LAWRENCE K. ALTMAN [NYT]
Medical dogma holds that damage to the heart is irreversible and that the body cannot
grow new cells to replace those that die from a heart attack or other heart ailment.
But new findings to be published today in the New England Journal of Medicine provide what
experts said was the strongest evidence reported that some human heart muscle cells did
regenerate after a heart attack, though generally too few to repair all the damage.
Using a high-resolution microscope and a new laboratory technique, a team led by Dr. Piero
Anversa of the New York Medical College in Valhalla has found evidence that the human
heart did grow new muscle cells after a heart attack.
The next stage of research is to find ways to tap the heart's growth reserve to better repair
damage from a heart attack and many other heart conditions, Dr. Anversa said in a telephone
interview from Naples, Italy, where he lectured on his findings yesterday.
Heart-cell regeneration research has been controversial. Because researchers had never found
evidence of heart-cell regeneration before, they came to believe that it did not occur. Scarring
that followed heart attacks suggested that the heart was unable to make new cells.
But Dr. Anversa had support for his views from some leading experts not involved with his
research who called the report "a landmark study." The experts said that the findings have
important implications for treating heart disease, the nation's leading cause of death.
"This is a breakthrough, at least for a new way of thinking about the heart's recuperative power
and ways to repair a damaged heart," said Dr. Valentin Fuster, a former president of the
American Heart Association.
With years of more research "you might have a new therapeutic weapon" for heart disease and
"the implications are incredible," said Dr. Fuster, who is chief of cardiology at Mount Sinai
Hospital in Manhattan.
Dr. Claude J. Lenfant, the director of the National Heart, Lung and Blood Institute in
Bethesda, Md., said that Dr. Anversa's findings "provide the most dramatic and clear-cut
demonstration to date of heart-cell regeneration after cardiac injury."
The findings, Dr. Lenfant said, add to those from studies on animals that show the dogma that
the heart cannot regenerate "is no longer true."
The institute, a federal agency, helped pay for the research by Dr. Anversa's group in Valhalla
and at the University of Udine and the University of Trieste in Italy.
Dr. Lenfant said the findings eventually could have "enormous public health value" if they led to
new therapies that delayed the onset of heart failure and prolonged life. Dr. Lenfant also said
he believed the research held greater hope for heart disease than gene therapy, which many
experts consider a highly promising route to new therapies. But, he warned, the therapies were
"not going to be here tomorrow."
Dr. Anversa said he never believed that the heart was an exception to the rule that cell
regeneration was essential to life. Nor did he believe, as the dogma held, that scarring after
heart attacks was evidence against the heart's ability to make new cells. Other organs, like the
skin, constantly grow new cells to replace old and damaged ones and still leave scars, Dr.
Anversa said.
He added that "it made no sense" to him that humans were born with a set number of heart
cells "that were able to contract 70 times a minute for more than 100 years without the
capacity for regeneration."
Until recently, medical dogma also held that the brain could not grow new cells. But recent
research activity has upset that belief.
New research by his and other teams shows that, with respect to its ability to make new cells,
"the heart is no different than any other organ," Dr. Anversa said. "The paradigm has to
change."
Dr. Anversa began this line of research 20 years ago. In its latest version, his team compared
muscle cells in the hearts of 13 patients who died 4 to 12 days after a large heart attack with
those in the hearts of 10 patients who died from other causes. Dr. Anversa's team focused on
two areas — the zone of tissue bordering the site of a heart attack and a more distant area of
the heart.
Dr. Anversa attributed his success chiefly to use of an old tool and a new technique. The old
tool is the use of a high-resolution confocal microscope that can provide resolution for up to
0.5 micrometers — less than 1200,000 of an inch. The new technique involves measuring the
activity of a protein, known as Ki-67, that is present in the nucleus of cells and is essential for
cell division.
Using the two methods and other standard ones like fluorescence staining, Dr. Anversa's team
found that the number of muscle cells, or myocytes, multiplying in diseased hearts was 4
percent in the border areas and 1 percent in distant areas, much higher than in normal hearts.
The technique is "solid," Dr. Fuster of Mount Sinai said.
Further calculations suggest that rapid growth of even a small number of new heart cells could
regenerate a large number of cells in three weeks.
The findings still leave researchers seeking answers to a number of crucial questions about the
origin of the new heart muscle cells Dr. Anversa identified. Were they cells in the heart that had
been awakened after sleeping for years, even decades, only by the crisis of a heart attack? Or
were the cells recruited from another site in the body in response to the heart attack?
Dr. Anversa said that his team had a good idea of where the new cells came from because it
had identified "pockets" of primitive cells with the characteristics of stem cells in the heart. But
he declined to disclose their precise location because he has not published the findings.
"We want to use what is in the heart to repair the heart" by promoting migration of large
numbers of new cells to repair the damaged tissue before it dies, Dr. Anversa said.
Such repair could extend beyond damage from heart attacks to that resulting from other
chronic conditions like untreated high blood pressure or cardiomyopathy, he said.
Dr. David Finkelstein, who directs basic heart research at the National Institute of Aging,
which helped pay for the research, said the new findings "may begin to clarify how hearts
respond to the normal insults of aging through previously undetected repair mechanisms."
Dr. Anversa added that "We have new hope to intervene in heart disease and repair what was
considered an irreparable problem — but I don't know how close we are to that." |
