November 17, 2002
IL (AHA) Ė Researchers have built
mechanically sound blood vessels out of tissue from human skin
cells, according to a study reported at the American Heart
Associationís Scientific Sessions 2002.
involves tissue engineering, an emerging science that takes
cells from the body, manipulates them in the laboratory to
create functional tissue, and puts the new tissue back into the
The goal is to
produce healthy, functioning blood vessels built exclusively
from a personís own cells, so the body's immune system won't
reject the new tissue. Such vessels would be important in heart
and leg bypass operations and for vessels called arteriovenous
shunts used for dialysis patients.
reported that tissue-engineered blood vessels didn't burst or
develop blood clots in laboratory tests and short-term animal
"The study's most
important findings were: First, the technology works from a
commercial perspective, meaning we can build mechanically sound
vessels for a wide array of patients using the exact same
protocol," says Todd McAllister, Ph.D., president and chief
executive officer of Cytograft Tissue Engineering in Novato,
Calif., which developed the vessel-building technique.
demonstrated that thrombogenesis (the formation of blood clots)
does not appear to be a problem in the short term Ė up to 14
days. Short-term blood clots are the biggest challenge facing
most synthetic materials, whether they are used for blood
vessels, new heart valves, or other vascular prostheses. We
expect to begin this research in humans within 18 months."
In the study
reported today, researchers took fibroblast cells from 11
patients (ages 54 to 84) with advanced cardiovascular disease
who had coronary artery bypass operations at Stanford
University. Fibroblasts form the outer wall of blood vessels.
The researchers used endothelial cells from animals to make the
inner lining of the vessels.
engineering involves growing cells on a synthetic scaffold to
create a specific shape, such as a piece of bone for use in
facial reconstruction surgery. These scaffolds have
traditionally been necessary to provide mechanical strength to
the new tissue.
Cytograft's chief scientific officer Nicolas L'Heureux, Ph.D.,
has developed a different approach called sheet-based tissue
"We can build a
tissue that is only a few hundred microns thick, the diameter of
several human hairs, that is robust enough that we donít need
synthetic materials or scaffolding to support it," L'Heureux
The cell sheets
are removed from the dish and wrapped around a temporary
stainless steel cylinder 4 millimeters (0.15 inch) in diameter.
The vessel then goes through a maturation phase where the
separate layers fuse into a homogeneous tissue.
the tissue from the steel cylinder, endothelial cells are seeded
to the inside to create the inner lining of the blood vessel.
Finally, the vessels are exposed to increasing rates of fluid
flow and pressure to precondition them for implantation.
vessels were implanted as a femoral (leg) artery graft in study
animals. The vessels were then removed at three, seven and 14
days after implantation. All but two of the vessels survived
past day three and seemed mechanically stable without forming
One question they
had going into this study is whether the same chemicals and
techniques that could successfully engineer tissue cells from
one human into a new blood vessel would also work on cells from
"It was quite
conceivable that differences from patient to patient would be so
significant that the same recipe for making blood vessels could
not be used in all cases," McAllister says. "We had no idea
whether we could do this across a wide range of age- and
evidence showing the vessels' reliability and clot resistance,
researchers plan to implant tissue-engineered blood vessels in
humans in 12 to 18 months, he says. The first patients will be
those with peripheral vascular disease, the severe blockage of a
leg artery that can lead to amputation.
Mark Koransky, M.D.; Nathalie Dusserre, Ph.D.; Gerhardt Konig,
B.S.; and Robert Robbins, M.D.