New protocol triples storage time for donated livers
Thursday, October 10, 2019
A three-step approach to the organ preservation process promises to help physicians store donated livers for hours longer than before. To this point, donated livers must be transplanted within nine hours of harvest. A varied protocol means livers may be viable for up to 27 hours.
Researchers at Massachusetts General Hospital and Harvard University experimented with ways to preserve livers longer by avoiding ice nucleation.
In previous studies, rat livers were preserved using a supercooling method that included a modified glucose compound. The combination prevented ice crystals from growing on the livers.
However, when the process was replicated for human livers, it didn't work. Since human livers are 200 times larger, the risk of heterogenous ice nucleation increased significantly. If ice grows on the organ, it cannot be used as a transplant.
"Delivering viable organs to matching recipients within the window of viability can often be the most challenging aspect of organ transplantation," said Seila Selimovic, Ph.D., director of National Institute of Biomedical Imaging and Bioengineering's Engineered Tissues program. "By giving doctors and patients more time, this research could someday affect thousands of patients who are waiting for liver transplants."
In the most recent study, published in the journal Nature in September 2019, researchers took a three-pronged approach to the problem. The first step was to prevent the storage solution from coming into contact with air.
Exposure to air greatly increases the chance of ice crystal formation. Therefore, the team removed air from the storage solution bag prior to supercooling a liver.
Next, two ingredients were added to the storage solution. Trehalose and glycerol protect and stabilize cell structure while also supporting the preservative properties of the other solution ingredients. Both additives have been used to cryogenically preserve cells in a lab setting but had not been used to preserve organs for transplant.
Finally, the team used machine perfusion to deliver the preservation solution to the liver. In the previous method, the solution is manually flushed through the liver tissue. Since the new solution is thicker, it can damage the cells lining the liver's blood vessels.
Machine perfusion delivers oxygen and nutrients to tissue capillaries while they're located outside the body. Researchers slowly lowered the temperature of the liver while increasing the concentration of the solution. This approach allowed the liver tissue to adjust and the solution to distribute more evenly throughout the organ.
"With supercooling, as the volume increases it becomes exponentially more difficult to prevent ice formation at sub-zero temperatures," said Dr. Reinier de Vries, a research fellow in surgery who worked on the study. "Before, there were a lot of experts who said, 'well this is amazing in small rats, but it will not work in human organs,' and now we have successfully scaled it up 200 times from rat to human livers using a combination of technologies."
A human liver treated in this manner has not been implanted, but this process will not negatively impact the organ.
"This new liver preservation method exemplifies National Institutes of Health's goal to foster the discovery and translation of innovative ideas," said Dr. Averell H. Sherker, NIDDK program director for liver diseases. "With further research, organs will be able to travel greater distances and benefit the most critically ill patients requiring liver transplantation."
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