Human derived stem cells can repair rat hearts damaged by heart attack
When human heart muscle cells derived from embryonic stem cells are
implanted into a rat after a heart attack, they can help rebuild the
animal's heart muscle and improve function of the organ, scientists
report in the September issue of Nature Biotechnology. 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. The findings suggest that
stem-cell-based treatments might one day help people suffering from
heart disease, the leading cause of death in most of the world.
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.
###
Public release date: 26-Aug-2007
Contact: Justin Reedy
jreedy@u.washington
206-685-0382
University of Washington
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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