X-Message-Number: 13054
From: Brent Thomas <>
Subject: research report -- liver cryobiology
Date: Tue, 4 Jan 2000 15:30:18 -0500 

interesting mainstream research that has possible cryonics implications:
                 Duke University Medical Center (http://www.mc.duke.edu)

                 Posted 1/4/2000

             Duke Study: Cold Needed To Preserve Livers
             For Transplant Also Can Kill Certain Cells 

             DURHAM, N.C. - A team of Duke University Medical Center
             has figured out why donated livers can suffer a mysterious
injury that damages
             their ability to perform well once transplanted. 

             They found out that the cold temperature needed to preserve one
set of
             specialized cells during the time the organ is out of a body is
actually producing
             a chain reaction that ultimately results in the death of a
different group of liver

             While the findings point to a possible drug to block this
process, the study
             suggests that liver transplant patients should not receive
platelet transfusions
             before their procedures, as some centers routinely do. 

             The cells in question are called sinusoidal endothelial cells,
highly specialized
             cells that appear only in the liver and which line the tiny
blood vessels that form
             a vast network throughout the organ. Researchers had known that
many of
             these cells become injured or die after the liver is
re-attached to its new blood
             supply in the transplant recipient, but they didn't know the
source of this
             "reperfusion" injury, which can impair liver function. 

             Immediately after removal from donors, livers are immersed in a
special cold
             solution to preserve the function of hepatocytes, cells who
have complex
             functions, producing as many as 5,000 different proteins.
However, the low
             temperature (1 degree C) required to effectively preserve
hepatocytes can also
             cause the sinusoidal cells -- which act as a detoxifying filter
between the blood
             and hepatocytes -- to become deformed. 

             Using a unique system in which blood is circulated through a
living and
             functioning liver outside a rat's body, the Duke researchers
found that the cells
             died from a process known as apoptosis, or programmed cell
death, and that
             the blood platelets initiated the apoptosis process. 

             "Our model showed that the longer the blood circulated through
the reperfused
             liver, the more platelets stuck to the sinusoidal cells," said
Dr. Pierre-Alain
             Clavien, lead researcher and chief transplant surgeon at Duke.
             analysis of the cells showed that platelets adhered to the
sinusoidal cells to
             trigger apoptosis. 

             "While we know that platelets are involved in clotting problems
in transplants,
             this study demonstrates another role for platelets in causing
problems in
             transplanted livers," he added. 

             The results of the study were published Thursday (Dec. 30) in
the January
             issue of the journal Gastroenterology. The first author of the
paper is Dr. David
             Sindram, also of Duke. 

             For transplant surgeons, the injury and death of the sinusoidal
cells is the most
             important reason for graft failure after transplantation and
one of the main
             challenges to be solved. In this regard, the surgeons face
somewhat of a
             paradox, according to the Clavien. 

             "On one hand, we must keep the liver cold, which lowers the
metabolic rate of
             the hepatocytes and preserves their function, but now we know
that there is
             something about the period of cold preservation that makes the
sinusoidal cells
             more susceptible to injury," Clavien said. "The cells do not
die until they come
             into contact with blood and oxygen, and then they die very

             While the researchers do not know for sure what it is about the
adhesion of
             platelets on sinusoidal cells that causes their death, the
studies do point to a
             possible target for therapeutic intervention. 

             "When we added a sugar that inhibits platelet adhesion to our
liver perfusion
             system, we found a significant reduction in the number of
platelets sticking to
             the sinusoidal cells," Clavien said. "In these particular
livers, there was also a
             corresponding significant reduction in the number of cells

             This suggests that there may be a drug or substance that can be
added to the
             solution used to preserve human livers that would keep
platelets from adhering
             to sinusoidal cells, Clavien said. Aspirin, for example,
inhibits platelet
             aggregation, but because of its blood-thinning properties, it
would not be
             appropriate for someone undergoing a transplant. 

             While a possible drug may come in the future, Clavien said
these findings
             should cause some centers to rethink their liver transplant

             "Since the liver transplant procedure can involve a lot of
blood loss, some
             centers give their patients platelets before surgery to offset
potential losses,"
             Clavien said. "Our data would suggest that this might not be

             While human livers remain viable outside the body in cold
solution for up to 30
             hours, liver surgeons know the sooner they can transplant the
organ into the
             recipient, the less injury the organ sustains. 

             Clavien's group is pursuing what signals the platelets are
sending to the
             sinusoidal cells to get them to commit suicide, as well as the
possible role of
             immune system cells in the blood and the sinusoidal cell

             The research was supported by a grant from the National
Institutes of Health
             and from the Duke University department of surgery. 

             Joining Clavien and Sindram in the study were Duke researchers
Dr. Robert
             Porte, Dr. Maureane Hoffman and Dr. Rex Bentley. Sindram is a
             fellow in Clavien's lab and is supported by the Leiden
(Netherlands) University
             Medical Center, the Netherlands Digestive Disease Foundation
and the
             European Society for Organ Transplantation. 

             Editor's Note: The original news release can be found at

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