Damaged heart? Grow around it!
Damaged heart? Grow around it!
(This article is scheduled for release in
the January, 2005 issue of the Harvard Heart
Letter. For more information or to order,
please go to http://health.harvard.edu/heart.)
Researchers are racing to heal injured
hearts by using stem cells from outside the
heart, and maybe even ones inside it.
An idea that was mere fantasy just a few years
ago - growing new tissue to replace damaged
or diseased heart muscle - is now one of the
hottest areas of on-the-horizon cardiology
research. Teams around the world are trying
to mend broken hearts by injecting or infusing
primitive stem cells or muscle cells into the
heart or by rousing the heart to repair itself.
Whether these efforts will pay off is anyone's
guess. The researchers must work their way
over daunting scientific, technical, and sometimes
ethical hurdles. Despite the occasional scientist's
overenthusiastic statement that such new therapy
will be routinely used in five years, it isn't
likely to get beyond clinical trials any time
It is easy to see why researchers, cardiologists,
and some businesspeople get excited about the
possibility of growing new, healthy heart tissue.
Take heart failure as a good initial application
of this effort. Dead muscle and scar tissue
left behind by a heart attack weaken the heart's
pumping ability, making it difficult for the
heart to deliver enough blood to meet the body's
demands. About five million Americans have
heart failure (23 million people worldwide),
half of whom die within five years. In the
U.S. alone, treating heart failure costs $40
billion a year.
Drugs and devices can ease symptoms and prevent
heart attacks or sudden death by reducing the
heart's workload, regulating its electrical
signals, and even assisting with some of the
pumping. What they don't do is reverse the
damage. In theory, growing new, healthy tissue
could give the heart the extra kick it needs
and eliminate some expensive and not always
A number of so-called lower animals are able
to repair serious damage or sprout new parts.
Dice a flatworm, let the pieces grow, and you'll
soon end up with dozens of identical flatworms.
Salamanders that lose a tail or leg grow a
new one. They can even replace a damaged or
partially amputated heart. The zebrafish, a
striped, 2-inch denizen of many fresh-water
aquaria, can do the same neat trick.
Humans aren't nearly so plastic. To be sure,
most cuts and scrapes heal perfectly. That's
a simple but effective form of tissue regeneration.
Our bodies can also repair damaged liver, bone,
and muscle tissue. Blow out your heart, though,
and your body could no more repair it than
your car could fix its own flat tire.
Yet studies beginning in the early 1980s indicated
that the heart may have some capacity for regrowth.
This set off a trickle of research that has
turned into a torrent of exploration.
Adding stem cells
Stem cells (A) taken from bone marrow,
thigh muscle, or the blood are infused
or injected into damaged heart tissue.
They take up residence (B) and grow
into healthy heart muscle (C).
Waking up stem cells
Growth factors, hormones, or other
substances (A) are infused or injected
into damaged heart tissue. They stimulate
dormant cardiac stem cells (B) to
multiply and grow into healthy heart
Stem cells to the rescue?
Each of us begins life as a single cell. That
cell becomes 2, then 4, 8, 16... At first,
these cells are identical, and each has the
potential to grow into a fully formed child.
Gradually, though, small clusters of cells
set off down separate paths, morphing into
the 200 or so different cell types that make
us "us". This process of specialization is
known as differentiation.
Small populations of cells remain partially
unspecialized. These are called stem cells.
Given the right chemical and genetic signals,
stem cells can develop into many different
cell types. Some live in bone marrow. Others
circulate in the bloodstream. And tantalizing
research suggests that some sit quietly inside
Now that scores of animal experiments have
shown that stem cells can be introduced into
the heart, researchers have moved on to trials
in humans. To date, more than 400 people have
received stem cell injections or infusions
(see figure). In general, the procedure improves
the heart's ability to provide the body with
oxygenated blood, and it may reduce the zone
of dead or inactive tissue after a heart attack.
Immature muscle cells called myoblasts may
be an alternative to stem cells captured from
bone marrow or blood. Myoblasts are harvested
from a marble-sized chunk of thigh muscle and
allowed to grow and divide for a few days to
increase their number. When injected into the
heart, they adopt the characteristics of heart
cells and begin to act like them.
Adding stem cells or myoblasts to the heart
isn't entirely without risk. Even though they
take up residence in the heart, they may not
fit seamlessly into its precise architecture.
This could interfere with the mustn't-fail
electrical connections that keep the heartbeat
steady. In fact, serious heart rhythm problems
have developed in a few people who received
stem cells or myoblasts.
The most flexible type of stem cell comes
from a fertilized egg that has divided a few
times. All of the cells in this pinhead-sized
ball, called a blastocyst, have the remarkable
ability to form any tissue in the body.
Because harvesting stem cells destroys the
embryo, research involving embryonic stem cells
has become entangled in the abortion debate.
The embryos used in this line of research
come from fertility clinics, which create more
fertilized embryos than can safely be implanted.
The unused ones are stored in case the couple
chooses to try to have another baby. Opponents
say that the use of embryonic stem cells destroys
human life. Supporters say that instead of
discarding unused embryos, those donated by
couples for stem cell research should be used
instead to help cure a variety of debilitating
yo ur own
Instead of injecting stem cells or myoblasts
into the heart, a handful of teams are pursuing
an even wilder idea - forcing the heart to
Biologists and cardiologists have long believed
that muscle cells in the heart, like nerve
cells, don't divide and can't repopulate a
zone of stressed, damaged, or dead tissue.
Researchers have been chipping away at that
notion for the past 20 years. We now know that
nerves in the brain can divide and grow, and
there is mounting evidence that heart cells
If there are, indeed, cardiac stem cells scattered
through the heart, it may be possible to prod
them into churning out legions of healthy cells
that are programmed to live and work in the
heart (see figure). Researchers are looking
for drugs, growth-factor cocktails, and other
chemical signals that might awaken dormant
cardiac stem cells.
Another self-repair strategy revolves around
an even more radical idea: coaxing some heart
cells to regress to a stem-cell-like state
and then stimulating them to make millions
of young, healthy heart cells. Dr. Mark Keating,
a cardiologist and molecular biologist at Harvard-affiliated
Children's Hospital, and his colleagues turned
back the clock for mouse muscle cells by bathing
them in fluid extracted from regenerating leg
of newt. The muscle cells lost their characteristic
shape and properties and became like stem cells.
This approach isn't nearly as far along as
stem cell therapy. But it could avoid some
of the risks seen with implanted stem cells
or myoblasts. That process is like "sending
a chic urbanite to live with a primitive tribe
in the Amazon - even if he managed to survive
and adapt, he would always stand out," says
Heart failure certainly isn't the only condition
that might benefit from stem cell therapy.
The approach is being tested for diabetes,
Parkinson's disease, spinal cord injuries,
Alzheimer's disease, and others. In the cardiovascular
realm, researchers are trying to create personalized
replacement heart valves covered with an individual's
own stem cells. Stem cell injections are also
being tested as a way to grow new blood vessels
around blocked coronary arteries.
The field of cardiac repair is in its infancy.
Early tests suggest that it's feasible to use
stem cells or myoblasts to heal a damaged heart.
What's needed now are long-term tests to show
how safe and effective these strategies are,
and whether it's possible to harness the heart's
own regenerative powers.
Several clinical trials are already under
way, and more are in the works. California's
controversial initiative to fund a decade of
stem cell research with $3 billion in state
money will undoubtedly help spur this research