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Dr. Laura Niklason, a researcher at Duke University, has grown artificial arteries in
the lab using cells from pigs and has successfully implanted the vessels back into the
animals. These arteries, unlike synthetic vessels, are the more appropriate size and
strength needed for heart bypass operations and are less likely to clog. Dr. Niklason's
discovery was published in the journal Science on April 16, 1999.
This development has significant implications for heart bypass surgery. Researchers
consider this a major step in the developing field of tissue engineering, where scientists
are trying to build viable artificial organs in the lab. "We're growing arteries in a
way that simulates the environment in the fetus when arteries normally develop," Dr.
Niklason said, explaining that the arteries take eight to 10 weeks to grow.
"Hopefully, this lays the groundwork for doing it in a patient."
Christine Schmidt, an expert in engineering artificial blood vessels at the University
of Texas in Austin, said researchers have been trying for more than a decade to do what
Niklason has managed. "Artificial arteries are what we consider the Holy Grail in the
field," Schmidt said. "It's important because ... there's not a good artificial
alternative for small-diameter arteries right now. For many years, people have tried
synthetics, and they don't work."
Artificial Arteries Pose
Potential Benefit to Coronary Bypass Surgery
Well over 600,000 patients a year in the United States and internationally receive
coronary bypass operations, according to the American Heart Association. During a coronary
bypass procedure, doctors take a vein (typically from the patient's leg) and graft it in
place of a clogged or diseased coronary artery. The grafted vessel routes blood around the
blockage in the diseased artery that is no longer properly feeding blood to the heart
muscle (myocardium). In normal use, veins are not as strong as arteries since they only
have to carry blood at a lower pressure. Thus, veins grafted in place of arteries
(especially the coronary arteries) can be damaged from the higher pressure they receive
when being used as arteries. In addition, some patients may suffer complications from the
loss of veins in their legs, and other patients don't have veins in good enough condition
for the bypass graft.
Dr. Niklason decided to get involved in tissue engineering while finishing her
residency at Massachusetts General Hospital in Boston. She approached Robert Langer, a
professor at the Massachusetts Institute of Technology, about joining his research lab.
She chose artificial arteries as her first project. Dr. Niklason likes to experiment and
felt tissue and blood vessel engineering was a task worth tackling. "When I started
this project, there were a lot of things I didn't know. ... I didn't know how cells grow
and behave in the lab," Dr. Niklason said. "But I figured I have a good general
background in medicine and fluid dynamics, so I could figure it out."
Niklason toiled with very few results for months. She took muscle cells from the
outside of pig arteries and set them growing on a tube-shaped synthetic scaffold. The idea
was that as the cells reproduced, the scaffold would dissolve, leaving a finished artery.
Two years into the project, the best she could create was an artery that would fall apart
at the touch of tweezers. "I had failure after failure after failure. It was pretty
discouraging," Niklason said. Eventually she created a device that helped the artery
grow thicker and produce collagen strands to make it stronger. A mechanical pump forces
red cell culture liquid through the artificial arteries at a rate of 160 beats a minute,
the same rate at which the heart of a fetus pumps and twice that of an adult heart.
Dr. Niklason promotes collagen growth by feeding the arteries each day with vitamin C.
She adds intermittent blue ultraviolet light that kills bacteria, since arteries developed
in a lab have no way of staving off infection. When the vessels are nearly grown, she
applies a different cell from the inside wall of a pig artery to the artificial vessel.
This last stage is critical to prevent clotting once the vessel is implanted. The results
are small, grayish white tubes with the elasticity of real arteries. They respond to drugs
much the same way that real arteries do. When the vessels were implanted in pigs, they
stayed free of clots for four weeks. Comparable vessels that were grown without liquid
being pumped through them began to clot much sooner.
The next steps: study the vessels
over a longer period and eventually try to replicate the research with human vessels
The next round of research will be to show what happens with the vessels over a much
longer period. "She's pushed things several steps beyond where they were
before," said Langer, a pioneer in tissue engineering. Niklason did much of her work
in Langer's MIT labs. "Previously most people had tried to grow arteries in static
conditions rather than design something that simulated the heart," Langer said.
Niklason brought her device and her research with her when she moved to Duke University to
take over a lab in September 1998.
While Niklason's research points a direction for doing the same thing in humans, it
could take years to develop a working model. Human cells do not grow in the lab as well as
pig cells. And cells from older people, those most likely to need bypass operations, are
even more difficult to grow. "There's no fundamental reason why it shouldn't
work," Niklason said. "But in research you learn not to guarantee
anything."
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