A recent study at the Medical Center may be the first step in improving the success of liver transplants. The study, which used a rat model, showed that the cold temperature required to transport livers for transplantation produces a chain reaction that ultimately causes the death of important cells called hepatocytes. Although researchers previously knew that some cells were damaged during transplantation, this study is the first that identified which cells were dying and why.
"[This research] provides further support for the concept that there are host factors that contribute to liver preservation injury," said Dr. Gregory Gores, professor of medicine at the Mayo Clinic's Division of Gastroenterology and Hepatology. The research may also explain why a transplanted liver often functions poorly after it is transplanted.
The findings, published in the January issue of the journal Gastroenterology, present a conflict for researchers who know that transplanted livers must be kept cold at the cost of losing other important cells.
"With anything good there are side effects," said lead researcher Dr. Pierre-Alain Clavien, professor of general surgery and chief transplant surgeon at the Medical Center. "Transplanted livers must be kept cold to preserve their functions, so if we can understand how [important] cells are injured, then we can try to block those mechanisms."
The research team used a unique system in which blood samples with and without platelets were circulated through healthy livers removed from rats' bodies.
At temperatures near freezing, platelets triggered the death, or apoptosis, of highly specialized cells called sinusoidal endothelial cells. Clavien said these cells appear only in the liver and line the tiny blood vessels that form a vast network throughout the organ.
"We found that platelets stick to endothelial cells [in prepared liver transplants] and trigger apoptosis of those cells in rats," he said.
He hopes to use this knowledge to understand liver grafts in humans, who exhibit known similar characteristics.
Clavien also believes the damaged endothelial cells may be correlated to the injury and death of another critical set of specialized cells called hepatocytes, which have complex functions including overseeing the manufacture of as many as 5,000 different proteins in the liver.
Clavien's ongoing research includes finding the molecules and mechanism by which platelets trigger endothelial apoptosis. In addition, the results of the study support the potential development of a drug that can hinder the apoptotic process initiated by the platelets.
However, until more research is conducted, Clavien suggests that physicians consider changing their transplantation protocol. For instance, he believes the study supports minimizing the administration of platelet transfusions to liver transplant patients, as some centers and clinics routinely do to offset the significant blood loss associated with liver transplants.
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