Supercooling tripled the shelf life of donor livers

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A new technique to
keep donor organs colder than ice cold could greatly extend the length of time
that those organs are viable for transplant.

Typically, donor
organs stay viable for several hours on ice at about 4° Celsius. Tissue can
last even longer at lower temperatures — but below zero degrees Celsius, the
formation of ice crystals risks damaging an organ and rendering it unusable.
Now, using chemicals that prevent an organ from freezing at subzero
temperatures, researchers have preserved five human livers at –4° C. That
supercool storage system tripled the livers’ typical
shelf life
from nine to 27 hours, researchers report online September 9 in Nature Biotechnology.

This kind of
deep-chill technology “would be huge for transplantation,” says Jedediah Lewis,
president and CEO of the Organ Preservation Alliance in Berkeley, Calif., a
nonprofit that supports research on organ and tissue preservation but was not
involved in this research.

Every year, thousands of donor organs are
discarded
for various reasons, including the inability to find a suitable
patient close enough to receive the organ before it goes bad. If donor tissue
were viable longer, doctors could get organs to patients who might otherwise be
too far away, Lewis says. That could lead to more lifesaving surgeries for
patients waiting for a transplant — currently more
than 100,000
in the United States alone. Pushing back organs’ expiration
dates could also curb the costs of private flights to rush organs between
cities and allow for more flexible surgery scheduling, Lewis adds.

In the new study,
researchers devised a cocktail of cryoprotectant chemicals, including trehalose
and glycerol, to combat ice formation and protect cells at extremely cold temperatures.
To ensure each liver was completely saturated with preservatives, the
researchers administered the chemicals using a machine perfusion system. That
device is basically “an artificial body for the liver” that pumps fluids into
an organ in a way that imitates blood flow, says Reinier de Vries, a medical
doctor and mechanical engineer at Harvard Medical School and Massachusetts
General Hospital in Boston.

This supercooling
preparation scheme is a more sophisticated version of a chemical injection
previously shown
to preserve rat livers
for several days at –6° C (SN: 7/3/14). Additional cryoprotectant chemicals and the more
elaborate machine perfusion equipment allowed the new setup to handle human
livers, which are harder to supercool because they’re about 200 times as big as
their rat counterparts. 

Once each human liver
was loaded up with cryoprotectants, de Vries and colleagues sealed it in a bag
to stash in a chiller at –4° C. After 20 hours in the icebox, the researchers
hooked the liver up to a machine perfusion system that flushed out the
chemicals that helped it withstand the cold and warmed the organ to room
temperature. From start to finish, the supercool storage process took about 27
hours.

In experiments with
five livers, “we got absolutely no ice formation for the duration of storage,”
says study coauthor Shannon Tessier, a biomedical engineer also at Harvard and
Mass General. When the researchers checked the livers for tissue damage and
compared how well the livers took up oxygen, produced bile and performed other
functions before and after supercooling, the team found no major changes in the
organs’ health. Tessier and colleagues then warmed three of these organs to
body temperature and infused them with red blood cells and plasma to simulate a
transplant, and all remained viable.

To validate the supercool
setup, the next step is to transplant organs stored at subzero temps into large
animals like pigs, Tessier says. “We actually want to show that the animals
survive transplantation,” she says. “Then, hopefully we can think about
clinical trials.”

The new supercooling technique “is a really elegant piece of work,” says Malcolm MacConmara, a transplant surgeon at the University of Texas Southwestern Medical Center in Dallas. He imagines that other organs, such as kidneys and hearts, may also benefit from this technology to curb organ shortages (SN: 3/12/19).

Postponing the best-by
times for donor organs may be especially useful for organs that deteriorate
even faster than the liver, says James Shapiro, a transplant surgeon at the
University of Alberta in Edmonton, Canada. “In heart transplants, they like to
keep their cold storage times very short — if they go beyond around four hours
or so, then the heart surgeons start to get very nervous,” he says. “If you had
a system like this that would facilitate longer storage times, you could really
open up the possibility of saving more lives.”

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