In a paper
published in the June 7 issue of the New England Journal of Medicine,
scientists from New York Medical College in Valhalla, NY report their
success in finding large scale replication of heart muscle cells in two
regions of the heart, and in identifying several other key indicators
of cell regeneration.
"It has
long been assumed that when the heart is damaged such as after a heart
attack heart muscle cells do not regenerate and the damage is permanent.
This assumption has been challenged in recent years by evidence that heart
muscle cells may in fact regenerate. Now, this latest research provides
the most dramatic and clear-cut demonstration to date of heart cell regeneration
after cardiac injury," says Claude Lenfant, M.D., director of the
NHLBI, a component of the National Institutes of Health.
"With
this landmark study, we have a new understanding of the heart that opens
up the possibility of repairing heart muscle damage after a heart attack,"
he adds.
"This
finding, if confirmed, may begin to clarify how hearts respond to the
normal insults of aging through previously undetected repair mechanisms,"
says David Finkelstein, Ph.D., director of basic cardiovascular research
at the NIA.
Piero Anversa,
M.D., professor of medicine and director of the Cardiovascular Research
Institute, and colleagues, studied myocytes (heart muscle cells) from
the hearts of 13 patients, 4 to 12 days after their heart attacks, and
from the hearts of 10 patients who did not have cardiovascular disease.
Samples were obtained from the border zone near the site of the heart
attack and from a more distant site from the damaged tissue.
these areas of the heart with a high resolution confocal microscope, Anversa
and colleagues were able to measure the expression of Ki67, a protein
found in the nucleus of dividing heart muscle cells. Ki67 is expressed
during all phases of a cell's life cycle and is a strong indicator of
cell division.
The scientists
also obtained images of mitotic division and found other evidence of myoctye
replication, including the formation of the "mitotic spindle,"
and "contractile ring," critical structural indicators of cell
division.
Important evidence
of myocardial repair was demonstrated by the mitotic index, a measurement
of the degree of myocyte division. In comparison with normal hearts, the
number of myoctyes multiplying in diseased hearts was 70 times higher
in the border zone and 24 times higher in the remote myocardium.
The next challenge,
according to Anversa, is to find the source of the dividing myoctyes.
"Are these cells a sub-population of known cells that retain the
capacity to divide, or are they multiplying cells that originate from
stem cells present in the heart?" he asks.
"There
are preliminary indications that primitive cells like stem cells exist
in the human heart. Stem cells may have the ability to develop into the
various cardiac cell types and form new healthy functioning myocardium.
If we can prove the existence of cardiac stem cells and make these cells
migrate to the region of tissue damage, we could conceivably improve the
repair of damaged heart muscle and reduce heart failure," says Anversa.
Research on
animal models supports this possibility. In the April 4 issue of Nature,
the Anversa team and a colleague at the NIH reported that adult stem cells
isolated from mouse bone and injected into a damaged mouse heart became
functioning heart muscle by developing into myocytes and coronary vessels.
Moreover, the
newly formed tissue partially restored the heart's ability to pump blood.
Although a
cardiac stem cell has not yet been identified, scientists have identified
a neural stem cell in the brain.
"Why not
the heart?" asks Anversa.
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