Liver transplantation is currently the only available treatment
for severe liver failure, but there arent enough donors to fill
the need. Researchers have now made transplantable liver grafts
for rats that may point the way toward a successful liver transplant
substitute for humans.
The decellularized livers retain their networks of blood
vessels. Image courtesy of B.E. Uygun.
Your liver's job is to help fight infections and clean your
blood. It also helps digest food and stores energy for when you
need it. People needing a liver transplant are placed on a national
waiting list kept at the United Network for Organ Sharing.
Their blood type, body size and severity of sickness all play
a role in when theyll receive a liver. Whole livers can come
only from people who have just died. Currently, theres an estimated
shortfall of about 4,000 livers per year.
Liver cell transplantation has shown some promise, but has limited
uses. To be successful, an artificial transplant must be sufficiently
large to provide enough liver function. That requires a network
of small blood vessels—called a microvascular network—to transport
oxygen and nutrients throughout the structure.
Decellularization—the process of removing cells from a structure
but leaving a scaffold with the architecture of the original
tissue—has shown some success in other organs. One group of scientists
reported the decellularization of an entire heart that preserved
the original architecture and microvascular network. A research
team led by Dr. Korkut Uygun at Massachusetts General Hospital
tried a similar approach for the liver. Their work was supported
by NIHs National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) and others.
In the June 13, 2010, advance online edition of Nature Medicine,
the team explained the process they developed. They used a gentle
detergent over 3 days to decellularize the liver while preserving
its structure. A matrix of proteins remained behind to hold the
livers shape. Using a dye, the researchers showed that the microvascular
network in each eerily translucent liver was intact.
The researchers were then able to successfully introduce functional
hepatocytes—a type of liver cell—back into the matrix. When they
tested the recellularized matrix, they found that it carried
out liver-specific functions at levels comparable to a normal
Grafts transplanted into rats maintained their functional hepatocytes
as well, for a few hours. The researchers note, however, that
successful engineering of an entire functional liver will require
other types of cells.
"As far as we know, a transplantable liver graft has never been
constructed in a laboratory setting before," Uygun says. "Even
though this is very exciting and promising, it is a proof-of-concept
study only. Much more work will be required to make long-term
functional liver grafts that can actually be transplanted into
That said, the study highlights the feasibility of using this
approach. There is currently a large pool of livers that are
unsuitable for transplantation, including livers from people
who have died of heart attacks. These could potentially be used
to make decellularized liver matrices.