Studeo
14th June 2010, 14:27
Monday, June 14, 2010
Old Livers Made New Again
Unhealthy organs provide a framework for growing replacement ones.
http://www.technologyreview.com/biomedicine/25538/?nlid=3105&a=f
By Lauren Gravitz
Scientists at Massachusetts General Hospital in Boston have taken the
first steps toward building functional, transplantable livers. In a
study in rats, published online today by Nature Medicine, the
researchers took donor livers, gently stripped them of their cells
while leaving other material intact, and then used the remaining
structure as a scaffold on which to grow healthy liver cells. The
result was a nearly complete organ that was transplanted into the rats
and remained functional for up to eight hours.
Liver disease is the 12th-largest cause of death in the United States,
while heart and kidney disease rank even higher. The symptoms of organ
failure can be treated to some extent, but the only cure is
transplantation, and there just aren't enough healthy donor organs to
go around. For decades, researchers have been working to build
replacements. But organs are complex systems, with a cell density and
blood-vessel system that are difficult to replicate.
The new technique, which was first demonstrated in hearts two years
ago, takes advantage of an organ's preexisting structure in all its
intricacy, and provides a use for unhealthy organs that could not
otherwise be used. "We try to resuscitate organs that would be
discarded and do things to make them transplantable," says Basak
Uygun, the paper's first author and a researcher at the Center for
Engineering in Medicine at MGH.
Other approaches for organ regeneration have varied widely, from
creating lab-made scaffolds to using ink-jet printers to create
three-dimensional tissue. But all of these methods try to mimic what
the body has already successfully created. The "decellularization"
technique capitalizes on that, removing what's broken and replacing it
with healthy new cells. "What we've done is basically take the
shortcut," says Korkut Uygun, the researcher at the Center for
Engineering in Medicine who led the work.
"This leapfrogs other approaches," says Stephen Badylak, a specialist
in tissue engineering at the University of Pittsburgh's McGowan Center
for Regenerative Medicine. "The beauty of this approach is that it
doesn't try to synthesize anything. It tries to isolate Mother
Nature's three-dimensional scaffold and take advantage of that. If
this can be translated to the clinic--and we're still a ways away from
that--it's a tremendous advance."
Uygun and her colleagues started with livers from rat that had died
from oxygen deprivation. They decellularized the livers with a
detergent, which killed off the remaining cells and removed their
debris. What remained was a delicate scaffold of proteins and sugars
and other extracellular structures, including blood vessel
architecture--the most complex aspect of the liver, the hardest to
duplicate, and the one most necessary for the survival of the new
cells. The scientists seeded the scaffold with liver cells isolated
from healthy rat livers, as well as endothelial cells to line the
blood vessels, and the result remained functional in culture for 10
days.
The researchers also transplanted two-day-old reconstructed livers
back into rats, connecting them to the animals' vascular system. After
eight hours, the livers continued to incorporate the animals' blood
flow and remained functional, something that had never before been
done with such a complicated engineered organ. "It is very promising
approach that will revolutionize the field of tissue engineering for
livers," Basak Uygun says. It's a particularly challenging organ,
because it requires constant and extensive blood circulation. "So if
this could be done for livers, it's major progress."
"It's very good work and it advances the field, showing more and more
that these things can in fact be done and are possible," says Anthony
Atala, director of the Institute for Regenerative Medicine at Wake
Forest University Baptist Medical Center, who has used both the
ink-jet printing and decellularization approach. "Solid organs are
incredibly complex, because they have a lot more cells per centimeter
than any other tissue type. And how do you get blood supply to such a
large volume of cells? Decellularized organs are a good strategy for
preserving vascular tissue."
There are, however, a few big obstacles remaining. The first problem
is that the current method can't quite repopulate the blood vessels
densely enough to allow blood circulation for more than 24 hours. The
exposed collagen of the scaffold causes the blood to coagulate and
clot, which is why Uygun left the engineered livers transplanted for
only eight hours.
The second obstacle will be finding a steady source for healthy human
liver cells. In the nearer term, the researchers believe they can rely
on cells from healthy donors. (Healthy livers can regenerate back to
full size within just a few weeks.) But further down the line,
stem-cell science may be advanced enough for people to donate their
own cells, allowing scientists to differentiate them in the lab into
liver cells that won't induce an immune-system reaction and use those
to seed a scaffold.
Korkut Uygun and his colleagues are already working on a solution to
the blood-vessel problem, and believe they should have fully
functional liver transplants in rats within two years. "We're hoping
it will be in the clinic in five to 10 years," he says. "That's
assuming nothing goes wrong."
It's a tantalizing prospect. "This represents a potential therapy for
those patients who aren't fortunate enough to get a transplant or
aren't eligible for one," Badylak says. "It's a terrific step
forward."
Copyright Technology Review 2010.
Old Livers Made New Again
Unhealthy organs provide a framework for growing replacement ones.
http://www.technologyreview.com/biomedicine/25538/?nlid=3105&a=f
By Lauren Gravitz
Scientists at Massachusetts General Hospital in Boston have taken the
first steps toward building functional, transplantable livers. In a
study in rats, published online today by Nature Medicine, the
researchers took donor livers, gently stripped them of their cells
while leaving other material intact, and then used the remaining
structure as a scaffold on which to grow healthy liver cells. The
result was a nearly complete organ that was transplanted into the rats
and remained functional for up to eight hours.
Liver disease is the 12th-largest cause of death in the United States,
while heart and kidney disease rank even higher. The symptoms of organ
failure can be treated to some extent, but the only cure is
transplantation, and there just aren't enough healthy donor organs to
go around. For decades, researchers have been working to build
replacements. But organs are complex systems, with a cell density and
blood-vessel system that are difficult to replicate.
The new technique, which was first demonstrated in hearts two years
ago, takes advantage of an organ's preexisting structure in all its
intricacy, and provides a use for unhealthy organs that could not
otherwise be used. "We try to resuscitate organs that would be
discarded and do things to make them transplantable," says Basak
Uygun, the paper's first author and a researcher at the Center for
Engineering in Medicine at MGH.
Other approaches for organ regeneration have varied widely, from
creating lab-made scaffolds to using ink-jet printers to create
three-dimensional tissue. But all of these methods try to mimic what
the body has already successfully created. The "decellularization"
technique capitalizes on that, removing what's broken and replacing it
with healthy new cells. "What we've done is basically take the
shortcut," says Korkut Uygun, the researcher at the Center for
Engineering in Medicine who led the work.
"This leapfrogs other approaches," says Stephen Badylak, a specialist
in tissue engineering at the University of Pittsburgh's McGowan Center
for Regenerative Medicine. "The beauty of this approach is that it
doesn't try to synthesize anything. It tries to isolate Mother
Nature's three-dimensional scaffold and take advantage of that. If
this can be translated to the clinic--and we're still a ways away from
that--it's a tremendous advance."
Uygun and her colleagues started with livers from rat that had died
from oxygen deprivation. They decellularized the livers with a
detergent, which killed off the remaining cells and removed their
debris. What remained was a delicate scaffold of proteins and sugars
and other extracellular structures, including blood vessel
architecture--the most complex aspect of the liver, the hardest to
duplicate, and the one most necessary for the survival of the new
cells. The scientists seeded the scaffold with liver cells isolated
from healthy rat livers, as well as endothelial cells to line the
blood vessels, and the result remained functional in culture for 10
days.
The researchers also transplanted two-day-old reconstructed livers
back into rats, connecting them to the animals' vascular system. After
eight hours, the livers continued to incorporate the animals' blood
flow and remained functional, something that had never before been
done with such a complicated engineered organ. "It is very promising
approach that will revolutionize the field of tissue engineering for
livers," Basak Uygun says. It's a particularly challenging organ,
because it requires constant and extensive blood circulation. "So if
this could be done for livers, it's major progress."
"It's very good work and it advances the field, showing more and more
that these things can in fact be done and are possible," says Anthony
Atala, director of the Institute for Regenerative Medicine at Wake
Forest University Baptist Medical Center, who has used both the
ink-jet printing and decellularization approach. "Solid organs are
incredibly complex, because they have a lot more cells per centimeter
than any other tissue type. And how do you get blood supply to such a
large volume of cells? Decellularized organs are a good strategy for
preserving vascular tissue."
There are, however, a few big obstacles remaining. The first problem
is that the current method can't quite repopulate the blood vessels
densely enough to allow blood circulation for more than 24 hours. The
exposed collagen of the scaffold causes the blood to coagulate and
clot, which is why Uygun left the engineered livers transplanted for
only eight hours.
The second obstacle will be finding a steady source for healthy human
liver cells. In the nearer term, the researchers believe they can rely
on cells from healthy donors. (Healthy livers can regenerate back to
full size within just a few weeks.) But further down the line,
stem-cell science may be advanced enough for people to donate their
own cells, allowing scientists to differentiate them in the lab into
liver cells that won't induce an immune-system reaction and use those
to seed a scaffold.
Korkut Uygun and his colleagues are already working on a solution to
the blood-vessel problem, and believe they should have fully
functional liver transplants in rats within two years. "We're hoping
it will be in the clinic in five to 10 years," he says. "That's
assuming nothing goes wrong."
It's a tantalizing prospect. "This represents a potential therapy for
those patients who aren't fortunate enough to get a transplant or
aren't eligible for one," Badylak says. "It's a terrific step
forward."
Copyright Technology Review 2010.