August 27, 2001
Research team fixes broken hearts with stem cells
By Sherry Baker
A high school track star suddenly collapses during practice, his heartbeat
inexplicably thrown into quivering, life-robbing chaos. How and why did
his heart suddenly produce the electrical storm of deadly, irregular beats
known as ventricular fibrillation, leading to sudden death?
This is the kind of mystery that could be unraveled in the Cellular Therapy
Center at the VA Hospital. Emory researcher Samuel Dudley and colleagues
Alice Huang and Mark Leimbach are working to unlock intracellular secrets
of heart function.
Dudleys team are the only scientists, as far as he knows, using
gene targeting to manipulate stem cells from mice into perfect replicas
of human cell mutations linked to arrhythmias. The result could be a new
model for the study of cardiovascular diseaseespecially genetic
disordersand offers new hope for innovative treatments and potential
Just the fact that heart cells are growing in the lab is remarkable.
Cardiac electrophysiology researchers, who study and map the electrical
landscape of the heart, have long been hampered by how quickly isolated
heart cells die in a culture dish. But Dudley and his colleagues have
developed techniques to overcome this problem.
We dont know exactly how this works yet and what all the
triggers are, but if we can understand how heart cells develop, then we
may be able to understand congenital heart defects, said Dudley,
assistant professor of medicine and physiology and chief of the VAs
Dudley currently is studying Long QT syndrome and Brugadas Syndrome
(also known as idiopathic ventricular fibrillation), two potentially deadly
autosomal dominant heart diseases.
These diseases have been hard to study, he said. To
do a clinical trial, you might have to find several families with this
particular mutation and follow them for many years, waiting for a cardiac
event. In the lab, we can see how heart cells with these mutations behave
in the context of a normal action potential within three weeks.
Although Long QT and Brugadas syndromes are relatively rare diseases,
Dudley said they may model more common acquired heart diseases. He and
his team are studying the genetic manipulation of stem cells with an eye
on additional future cardiac therapies, including growing replacement
tissue for damaged hearts.
The researchers want to see if placing genetically altered cells in hearts
can increase the strength of the organ and possibly repair the interior
surface areas, or epithelium, of vessels injured by balloon angioplasty.
Cell therapy also may prove useful in helping to prevent or alter restenosis,
the reclogging of vessels after theyve been opened by angioplasty.
Dudley feels stem-cell technology is even more promising than genetic
therapy. We can alter the genome of these cells before putting them
into peopleand we can do it in the culture dish, where we know exactly
what weve done, he said. Unlike genetic therapies so
far, this is a long-lasting change. We can even design cells sensitive
to a certain medication so we can make sure the altered cells die on command
if something goes wrong.
Another advantage is the high likelihood that these cells, which do not
express the immunologic markers associated with rejection, can be transplanted
successfully from animals to humans. The potential donor population
is very great, Dudley said.
In fact, Dudley questions whether stem-cell research might hold the key
to why humans ageand how the process might be altered.
In theory, aging is a stem cell function disorder, he said.
It is becoming clear that the number of stem cells you have decreases
by about 10 percent every decade of life. By the time you get to fairly
old adulthood, you dont have too many. So maybe the reason we all
break down as we get older is that we dont have enough stem cells
floating around to fix us up again.
Theres the possibility we could take stem cells out of your body, propagate them in the lab and expand them, then freeze them until you need them. Im convinced that in the long term, this technology has an extremely high potential to alter not only cardiology therapies, but the basic landscape of medicine.