Adult Stem Cells Help Weakened Hearts

Even patients who suffered an episode decades ago can
benefit, researchers say. By Karen Kaplan and Alan Zarembo
Times Staff Writers

September 21, 2006

Using stem cells harvested from patients' own bone marrow,
researchers improved cardiac function in heart attack
patients months, years — and even decades — after the
attacks, they reported Wednesday.

The infusion of stem cells boosted cardiac pumping
efficiency by 7% in three months — a modest gain, but still
a significant improvement for a chronic condition.

In one case, a patient who had suffered a heart attack 30
years earlier showed an 11% improvement after the
treatment, according to the study in the New England
Journal of Medicine.

The German researchers also found tentative signs that
patients could continue to improve with repeated
treatments.

"We have always thought that a heart attack is permanent
damage, but now there is the potential that this damage can
be repaired," said Dr. Christopher P. Cannon, a
cardiologist at Brigham and Women's Hospital in Boston who
was not involved in the research.

Though the researchers are uncertain why the therapy works,
the findings are a sign that the long-touted regenerative
powers of stem cells may be gradually moving from the
laboratory into viable human therapies.

Some researchers cautioned that it was too soon to say that
the results could be translated into a routine treatment.

"There are a number of therapies that have gotten to this
step but when subjected to more rigorous trials have not
worked," said Dr. Gregg C. Fonarow, a professor of
cardiovascular medicine at UCLA.

But Dr. Andreas M. Zeiher, chair of the department of
medicine at Johann Wolfgang Goethe University in Frankfurt
and senior author of the study, said the preliminary
results pointed to potential new strategies for treating
chronic heart disease, for which there is no cure.

Stem cells present one of the most tantalizing mysteries in
medicine. One form, known as embryonic stem cells, are
capable of generating any type of tissue in the body, but
scientists haven't learned the biochemical means to
transform them.

The current study focused on a second type of cells known
as adult stem cells. There are many types, each focused on
regenerating a specific group of tissues to help the body
repair normal wear and tear.

Stem cells from bone marrow have been used for decades to
regenerate blood and immune cells in cancer patients.
Laboratory experiments suggest that these cells also can
make heart muscle, blood vessels, nerve cells and other
tissues.

The advantage of bone marrow stem cells is that they are
easy to extract and can be collected from the same patients
they will be used to treat, avoiding problems of tissue
rejection.

Heart disease has been one of the primary targets of stem
cell research.

One of five deaths in the United States is caused by a
heart attack, which occurs when heart muscle is deprived of
blood and dies. About 1.2 million heart attacks occur in
the United States every year, leading to nearly 500,000
deaths, according to the American Heart Assn.

The German researchers recruited 75 patients who had
suffered a heart attack at least three months — and as long
as 30 years — earlier.

The patients were already receiving state-of-the-art drug
treatments for their heart disease, including the use of
beta blockers and cholesterol-lowering statins.

The researchers extracted 50 milliliters of bone marrow
from the patients' hips. They isolated a soup of cells that
included the stem cells and infused it into patients within
a matter of hours.

The researchers divided the patients into three groups. One
received the bone marrow stem cells and another was treated
with different stem cells derived from their own blood. A
third group served as a control.

Three months later, the researchers tested the patients'
left ventricular ejection fraction, a measure of how much
oxygenated blood is pumped into the circulatory system. In
healthy people, it ranges from 57% to 75%.

The patients in the study started out with ejection
fractions that averaged from 39% to 43%.

Those treated with bone marrow stem cells saw their
heart-pumping efficiency increase over three months by an
average of 2.9 points — a 7% improvement.

Over the same period, patients in the control group saw
their pumping efficiency decline by an average of about 3%,
and those treated with blood stem cells dropped about 1%.

To confirm their findings, the researchers swapped the
treatments and gave patients in the control group either
blood or bone marrow stem cells. Again, the patients who
got bone marrow cells saw an increase in their pumping
efficiency.

Fonarow of UCLA said the improvement was similar to the
effect of statins, which boost pumping efficiency by 5% to
8%.

The patients treated with bone marrow cells showed an
increased ability to tolerate physical activity before
becoming tired or breathless — and the improvements have
been sustained, Zeiher said.

He said one patient who had suffered a heart attack four
years earlier improved by 61% and returned to the golf
course to play at least nine holes.

"For the past 20 years, we have obsessed about treating
[heart attacks] quickly — time is muscle," said Dr. Douglas
Losordo, chief of cardiovascular research at St.
Elizabeth's Medical Center in Boston. "What this paper
tells us is there is another time window for therapeutic
intervention that's quite a bit longer and larger than we
thought."

Dr. Anthony Rosenzweig, director of cardiovascular research
at Beth Israel Deaconess Medical Center in Boston, said the
results suggested the stem cells were doing more than just
accelerating the recovery process.

It had been six years on average since these patients had
their heart attacks, he said. "If it were just hastening
healing after a heart attack, you wouldn't necessarily
predict you'd be able to have a beneficial impact so long
after."

Laboratory experiments have shown the cells can rebuild
damaged heart cells, stimulate the formation of new blood
vessels and release chemicals that aid the healing process,
Zeiher said. Some doctors, however, noted that a key piece
of information was missing from the study: What exactly
were the bone marrow cells doing inside the heart?

"They provide no evidence that the injected [stem cells]
actually settled in the heart," Dr. Robert S. Schwartz,
deputy editor of the New England Journal, wrote in a
perspective piece accompanying the study. He added in an
interview: "Physicians should know how any therapy they
give works. That's fundamental."

Others found the mystery less bothersome.

"We still don't know how statins work, but I haven't
stopped prescribing them," Losordo said.

The German researchers also published results of a
companion study showing that patients who received bone
marrow cells within seven days of a heart attack improved
their blood-pumping efficiency by 11% after four months,
compared with a 6% boost for patients who got a placebo.

A third study, conducted by researchers in Norway, found
their stem cell method provided no improvement, although
the study was not precise enough to detect the small
increases in pumping efficiency reported by the German
team.