‘Supercooling’ dramatically extends life of transplanted organs (Wired UK)


A supercooled rat liver sits in the preservation solution in the machine perfusion system.
A supercooled rat liver sits in the preservation solution in the machine perfusion system.Wally Reeves, Korkut Uygun, Martin Yarmush, Harvard University


A team of tissue engineers has
shown that a rat’s liver can remain viable for four days outside of
the body, using a new “supercooling” technique.

Cooling donor organs in ice and a special solution can help
ensure they last long enough to transport them to a recipient.
However, those timings vary hugely and put constraints on medical
teams to rush the procedure while it remains in a very narrow
window of viability. For instance, while kidneys can last around 24
hours, hearts and lungs have a survival time outside the body of
around five hours.

A team from the Centre for Engineering in Medicine at
Massachusetts General Hospital opted to trial a new preservation
technique with livers, which tend to last around 12 hours after
extraction. Of course, the experiments were done with rats. But the
team is hopeful the results can be replicated in larger animals
and, one day, humans.

The technique — which stands to revolutionise organ
transplantation, giving medics the opportunity to prepare longer
and reach people further away — begins with machine perfusion.
This is a technique commonly used for kidney transplants, whereby a
cool solution is pumped through the organ to keep it actively
functioning outside the body. It allows the organ to keep getting
oxygen and nutrients, so cell death is delayed. The team modified
the process by using a specially tailored glucose compound — one
part remains in the liver cells and acts as a barrier against the
cold, the other part of the compound (essentially anti-freeze)
keeps the cell membranes cool.

The organs were then cooled to -6C, but the solution ensured the
cells did not actually freeze — they just remained
“supercooled”.

When this technique was used for 72 hours, all the rats that
received that transplant lived for at least three months. However
when attempts were made to keep them viable for four days, survival
rates among those that received the organs dropped to 58 percent.
It’s still a huge improvement upon traditional techniques
— any rat receiving an organ preserved for three days using
those methods did not survive.


The liver is perfused with a solution in this pump system before and after supercooling preservation. The blue colour is caused by antifreeze that surrounds the components of the system to regulate the temperature.

Wally Reeves, Korkut Uygun, Martin Yarmush, Harvard University


“We have shown that each of these components is individually
required to achieve viable supercooling preservation in our model,
as evidenced by long-term recipient survival,” the team writes in
Nature Medicine. This was proven when elements of the
coolant compound or the machine perfusion were taken away –
without all the elements in place, and the precise temperature
maintained, the rats did not survive with organs preserved for
these longer timeframes. 

“To our knowledge, supercooling is the first preservation
technique capable of rendering livers transplantable after four
days of storage,” the team writes. “As extensive screening of
different additives or variations in protocol is still ongoing,
additional improvements could be achieved from future
experimentation.”

The authors do admit that the study exists only as a
proof-of-concept — a rat is not a particularly great model for
complex human organs and their preservation. “The size, robustness
and preservation properties of human hepatocytes and livers differ
from those of rodents, presenting translational challenges not only
regarding preservation biology, but also engineering and cost.”

The plan next time around is to trial the approach in bigger
animals, said Rosemarie Hunziker, program director of Tissue
Engineering and Regenerative Medicine at NIBIB, the body supporting
the research.

“It is exciting to see such an achievement in small animals, by
recombining and optimising existing technology,” she said. “The
main point here is that using all of these approaches at once was
what led to success. Halfway measures did not do. Such a tour de
force reflects this team’s very deep understanding of the complex
processes at work here, and how they relate simultaneously to each
other.”

Last year another method for keeping the human liver viable for
longer was proposed — but this time around trials did actually
involve a human liver that was successfully transplanted. OrganOx circulates red blood cells to keep nutrients and oxygen
flowing. Using this technique, keeping the organ at room
temperature, the liver remained viable for 24 hours, and two
patients have received one preserved in this way. 

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Source: wired.co.uk
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