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Reuters Health Information: Supercooling might extend preservation time of human livers for transplant

Supercooling might extend preservation time of human livers for transplant

Last Updated: 2019-09-16

By Will Boggs MD

NEW YORK (Reuters Health) - Supercooling of human livers might extend their preservation time beyond 24 hours, researchers report.

"To me, the most interesting result is that we were able to successfully supercool human livers and store them completely free of ice," said Dr. Reinier J. de Vries of Harvard Medical School and Massachusetts General Hospital, in Boston.

"There is a dire need for extended preservation, and although subzero organ preservation theoretically is a very promising solution, it has been an elusive goal for decades which was primarily hindered by injury due to ice formation," he told Reuters Health by email.

Dr. de Vries and colleagues previously showed that supercooled ice-free storage at -6C could extend viable preservation of rat livers.

In the current study, they used an improved supercooling protocol aimed at avoiding freezing in human livers by minimizing favorable sites of ice nucleation and preconditioning with protective agents during machine perfusion at 4C, followed by subnormothermic machine perfusion (SNMP) at -4C.

The supercooled human livers showed no significant changes in energy charge, bile production, portal and arterial resistance, oxygen uptake rate, or lactate levels after SNMP.

Moreover, hepatocellular injury was the same and stable before and after supercooling, as demonstrated by aspartic aminotransferase, alanine aminotransferase and potassium concentrations in the perfusate, the researchers report in Nature Biotechnology, online September 9.

After 20 hours of SNMP, three of the five livers underwent two hours of additional ex vivo normothermic reperfusion as a model for retransplantation. Further analysis demonstrated preserved mitochondrial and liver function.

Histology of these reperfused livers showed preserved lobular architecture with patches of reversible hepatocellular injury, along with focal spots of hepatocyte dropout in the pericentral zone that correlated to the initial histology of the liver graft.

"We need to develop an integrated device which is transportable and can be brought with the procurement team to the donor hospital," Dr. de Vries said. "With this device, we want to study the effects of supercooling preservation when it is initiated directly after procurement of the graft. In the current study, the organs were first transported to our center on ice for logistical reasons. We anticipate that if we replace this period of static cold storage at +4C by subzero supercooled storage, we can prolong the preservation duration even longer."

"Also," he said, "we need to confirm safety and evaluate the long-term viability of the supercooled organs after transplantation in a large-animal study with long-term follow-up."

Dr. Paolo Martins of the University of Massachusetts, in Worcester, who recently reviewed liver ex situ machine-perfusion preservation, told Reuters Health by email, "This has to be tested in an animal transplant model to assess if the grafts are really able to sustain life. One thing is to show that the liver is 'viable' by showing that the cells are alive and metabolism is present. To show that the liver can sustain life and the outcomes are similarly good or better than that of other preservation modalities is much harder."

"The issue of toxicity using 'anti-freeze' agents is not resolved," he said. "It is still one limitation of this approach. The simple tests (the authors) used cannot completely exclude a deleterious effect of this approach."

"This procedure seems more complex and costly compared with standard preservation," Dr. Martins said. "Until other groups independently show similar results, there is always a question about feasibility."

SOURCE: https://go.nature.com/2lNLZKd

Nat Biotechnol 2019.

 
 
 
 
                               
 
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