November 17, 2002
IL (AHA) – Preliminary findings of a
study in rats suggests that a person’s own cells might one day
replace artificial pacemakers, researchers reported at the
American Heart Association's Scientific Sessions 2002.
at Children’s Hospital Boston tested the ability of immature
skeletal muscle cells to interconnect with heart cells and
spread the electrical impulses that keep the heart beating
"The cells have
survived in rats for more than a year and they appear to have
made connections with cardiac cells," says Douglas B. Cowan,
Ph.D., a cell biologist who led the study. "The electrical
pathway developed within 10 weeks of implantation.
maybe a decade down the road – we may be able to use such
cell-based technologies in humans to free them from cardiac
pacemaker devices," says Cowan, also an assistant professor of
anesthesia at Harvard University Medical School in Boston.
starts with an electrical signal that begins in the atrium, a
tiny area of the heart’s upper-right chamber. The signal then
moves to the other chambers. Damage to the electrical pathway
between the atrium and ventricles (the lower chambers) can
result in complete heart block, a potentially fatal condition
that can only be treated by implanting a cardiac pacemaker.
"We have gathered
preliminary evidence that immature skeletal muscle cells can
establish a pathway to transmit electrical signals from the
heart’s upper right chamber to its lower right chamber," he
Heart block is
present in about one in 22,000 births, Cowan says. It also can
result from open-heart surgery in children, or develop later in
life. It’s particularly difficult to treat in infants and
children, he says.
"You can't feed
pacemaker wires through the blood vessels of some pediatric
patients because the vessels are too small," he explains.
The wire must be
coiled inside the chest so it can expand as the child grows, and
the pacemakers or their wires often fail, which results in
usually face several repair or replacement operations over the
course of their lives," Cowan says.
extracted small amounts of skeletal muscle from the rats to
obtain myoblasts, immature cells destined to become muscle.
Unlike mature skeletal muscle cells, myoblasts can make the same
proteins that heart muscle cells use to connect with one another
to transmit electrical signals.
The team used
engineered tissue containing about 70 percent myoblasts and 30
percent other cell types, using the connective tissue called
collagen. Tissue engineering involves removing cells from the
body, manipulating them in the laboratory to create a specific
tissue, such as a piece of bone for reconstructive surgery, and
implanting it into the patient.
The team created
three-dimensional strips of tissue by growing the cell mixtures
in small tubes cut in half lengthwise. They then surgically
implanted the strips in rat hearts.
"We used a
general shape and cells from other animals, but the idea is that
eventually we could custom grow tissue for a person using his or
her own cells,” Cowan notes. By using the patients’ own cells,
clinicians may avoid the risk that t he immune system will
attack the implanted cells, he says.
theoretical weakness in this idea was that the proteins required
to connect one heart cell to another – called connexins – are
usually not expressed in mature skeletal muscle," Cowan says. "Connexins
are very important to conduction in the heart. They modify the
speed and direction of the electrical signals, and greatly
influence how they flow from cell to cell."
question was whether these cells would actually connect with
cardiac cells to form an electrical pathway," he says.
research team reported that the pathway developed and the
connexins were present and functioning in the implanted tissue
more than one year later.
"We are now using
much more sophisticated measurements to confirm this phenomenon
and everything at this point shows that the electrical pathway
is there," Cowan says.
A lot of work
remains before researchers can test the cell-implant technique
in humans, Cowan says. "We need rigorous, state-of-the-art
experiments to confirm that the tissue is functioning and that
the same thing can happen in larger animals."
Yeong-Hoon Choi, M.D.; Christof Stamm, M.D.; Mara Jones, M.S.;
Francis X. McGowan, Jr., M.D.; and Pedro J. del Nido, M.D.