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Senior Citizen Health & Medicine
Human Stem Cells Successfully Repair Damaged Hearts
in Rats
Human trials could begin in about two
years, says researcher
Aug. 27, 2007 Clinical trials with humans could
begin in about two years to test the ability of embryonic stem cells
to rebuild heart muscle damaged by a heart attack and improve the
hearts function, according to a leader in recent research that was
successful using human stem cells to repair the hearts of rats. The
findings increase the possibility that stem-cell-based treatments may
one day help people suffering from heart disease, the leading cause of
death in most of the world.
The researchers also developed a new process that
greatly improves how stem cells are turned into heart muscle cells and
then survive after being implanted in the damaged rat heart. Their
report appears in the September issue of Nature Biotechnology.
The study was conducted by researchers at the
University of Washington School of Medicine in Seattle and at Geron
Corp. in Menlo Park, Calif. The scientists set out to tackle two of the
main challenges to treating damaged hearts with stem cells: the creation
of cardiac cells from embryonic stem cells, and the survival of those
cells once they are implanted in a damaged heart.
"Past attempts at treating infarcted hearts with
stem cells have shown promise, but they have really been hampered by
these challenges," explained Dr. Chuck Murry, director of the Center for
Cardiovascular Biology in the UW Institute for Stem Cell and
Regenerative Medicine, and corresponding author on the study.
"This method we developed goes a long way towards
solving both of those problems. We got stem cells to differentiate into
mostly cardiac muscle cells, and then got those cardiac cells to survive
and thrive in the damaged rat heart."
Embryonic stem cells can differentiate, or turn
into, any type of cell found in the body. But researchers had struggled
to get stem cells to differentiate into just cardiomyocytes, or heart
muscle cells -- most previous efforts resulted in cell preparations in
which only a fraction of 1 percent of the differentiated cells were
cardiac muscle cells.
By treating the stem cells with two growth factors,
or growth-encouraging proteins, and then purifying the cells, they were
able to turn about 90 percent of stem cells into cardiomyocytes.
The researchers dealt with the other big challenge
of stem cell death by implanting the cells along with a cocktail of
compounds aimed at helping them grow. The cocktail included a growth
"matrix"-- a sort of scaffolding for the cells to latch on to as they
grow -- and drugs that block processes related to cell death.
When using the pro-growth cocktail, the success
rate of heart muscle grafts improved drastically: 100 percent of rat
hearts showed successful tissue grafts, compared to only 18 percent in
grafts without the cocktail.
"The problem of cell death is pretty common in
stem-cell treatments," Murry explained. "When we try to regenerate with
liquid tissues, like blood or bone marrow, we're pretty good at it, but
we haven't been very successful with solid tissues like skeletal muscle,
brain tissue, or heart muscle. This is one of the most successful
attempts so far using cells to repair solid tissues -- every one of the
treated hearts had a well-developed tissue graft."
When the researchers followed up on the stem-cell
treatment by taking images of the rat hearts, they found that the grafts
helped thicken the walls that normally stretch out after a heart attack
and cause the heart to weaken. The thickened walls were also associated
with more vigorous contraction.
"We found that the grafts didn't just survive in
the rat hearts -- they also helped improve the function of the damaged
heart," said Dr. Michael Laflamme, UW assistant professor of pathology
and the lead author of the study.
"That's very important, because one of the major
problems for people suffering a myocardial infarction is that the heart
is damaged and doesn't pump blood nearly as well. This sort of treatment
could help the heart rebound from an infarction and retain more of its
function afterwards."
The next step in studying stem-cell treatments for
the heart is to conduct similar experiments in large animals, like pigs
or sheep, while further refining the treatment in rats.
Early human clinical trials could begin in about
two years, Murry said.
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