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Functional Arteries Grown from Cells Using Novel System that Simulates Fetal Environment

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Duke Health News 919-660-1306

DURHAM, N.C. -- A Duke University Medical Center researcher,
using a novel "bioreactor" system that mimics the fetal
environment, has used cells taken from adult pigs' arteries to
grow blood vessels that look and act like the real thing.

When implanted back into the same animals, the arteries
functioned much like native vessels, said Dr. Laura Niklason,
who published the results of her team's experiments in the
April 16 issue of the journal Science.

While there are many biological and technical hurdles to be
overcome before such an approach could be considered for use in
humans, such as to treat heart disease, the researchers said
this development represents a significant advance in the field
of tissue engineering.

"We are very excited that after many years, we have produced
a bio-engineered tissue that appears functional in animals,"
said Niklason, an anesthesiologist and bioengineer at Duke.

The engineered vessels, which were grown in a bioreactor
that provided nutrients and pulsed the growing vessels much
like a heart would, were as strong as native vessels, could
hold a suture without ripping and responded to drugs in much
the same manner as native vessels would.

The series of experiments was funded by two grants from the
National Institutes of Health and one from the Foundation for
Anesthesia Education and Research.

"While we still have much work to accomplish before moving
into human studies, these results not only demonstrated the
feasibility of culturing autologous arteries, but also that the
pulsatile approach was very effective," Niklason said.

To create the arteries, Niklason fashioned a tube from a
thin sheet of a biodegradable polymer which, like a sponge, is
97 percent air. Smooth muscle cells were collected from the
animal arteries and were impregnated throughout the polymer
tube. Once placed within the bioreactor, the tube was bathed
with similar nutrients found in native vessels.

"The bioreactor pulsed the nutrient solution through and
around the tube, approximating as much as possible the
conditions that exist within the developing animal fetus,"
Niklason said.

After eight to 10 weeks within the bioreactor, the smooth
muscle cells proliferated and filled all the spaces within the
polymer scaffolding, most of which had dissolved by that time.
To complete the artery, Niklason then added endothelial cells,
which line the interior of blood vessels, to the inside of the
tube. Several days later, the arteries were ready for
implantation back into the pigs.

"To the naked eye, the vessels looked exactly like native
vessels," Niklason said. "The surgeons who sewed them in told
me the way they held a suture was also comparable.
Additionally, the arteries also withstood blood pressures the
same as native vessels."

To see if arteries grown in the pulsing environment worked
better than those grown in a static system, Niklason implanted
arteries grown both ways back into the pigs. She followed their
performance for four weeks.

"While all the vessels remained open after two weeks, the
non-pulsed vessels began to show signs of thrombosis (clotting)
by the third week," she said. "The pulsed vessels remained open
for the four weeks."

Niklason conducted the bulk of her experiments while she was
research affiliate at the Massachusetts Institute of Technology
in the lab of Dr. Robert Langer, one of the leading researchers
in tissue engineering.

"This is certainly a major advance," Langer said. "Most
tissue culture systems are static - Dr. Niklason has taken it
one step farther and made a system that acts like a living
body. The bioreactor she developed demonstrates that we can
begin to grow cells and tissues in a more physiological way
outside the body.

"This very innovative approach to tissue engineering will
set the stage for future advances," he added. "Dr. Niklason and
others are bringing the field to the point where we will be
able to solve more complex problems."

Both Langer and Niklason are quick to point out that it is
too early to determine if and when bio-engineered blood vessels
will become a clinical reality. The major problem facing
researchers is that while pig smooth muscle cells grow easily
and rapidly outside the body in tissue culture, similar human
cells are more difficult to grow, Niklason said.

Also, Niklason pointed out, while the cells used to grow the
arteries are from the same animal that ultimately receives the
artery, the culture process may change them. Further studies
will need to be conducted on how the body will react to these
cells, which tend to be more immature than their native
counterparts.

The most obvious initial use of bio-engineered vessels would
be in peripheral or coronary artery bypass surgeries, where
veins are used to carry blood around clogged arteries. Because
veins are physiologically different than arteries, they are not
ideal candidates for bypass. Also, because of co-existing
diseases which effect blood vessels, many heart patients do not
possess sufficient veins for bypass procedures.

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