helps cool donor livers
to temperatures below 0ºC without freezing the liver tissue. This will increase
the availability of healthy livers for transplantation,
, as well as reduce the time constraints faced by the teams
involved in procuring and transporting the donor livers.
‘‘Super-cooling’ donor livers to sub-zero temperatures significantly extend the time they remain viable for transplantation at distant places without having to worry about damage to the organ.’
The study was conducted
by a team of researchers at the Massachusetts General Hospital, Boston, MA, USA
research findings have been published in the journal Nature Biotechnology.
The study was led
by Dr. Korkut Uygun, PhD, who is an Associate Professor of Surgery
(Bioengineering) at Harvard Medical School. He is also Director of the Cell
Resource Core at Massachusetts General Hospital and Director of the Organ
Reengineering Laboratory at the Center for Engineering in Medicine,
Massachusetts General Hospital, Boston, MA, USA.
members included Dr. Shannon N. Tessier, PhD and Dr. Reinier Johan de Vries,
MD. Dr. Tessier is an Investigator at the Center for Engineering in Medicine
and an Instructor in Surgery (Bioengineering) at Harvard Medical School and
Massachusetts General Hospital, Boston, MA, USA.
Dr. de Vries was
the lead author of the paper. He is a Research Fellow in Surgery at the Center
for Engineering in Medicine, Massachusetts General Hospital, Boston, MA, USA.
There were several other members of the study team, who were from the
University of Amsterdam in The Netherlands.
What is the Current Status of Liver
Transplantation in the US?
Liver transplantation is the procedure by
which a diseased liver in a person (recipient) is replaced with a healthy liver from another
person (donor). The donor’s liver is
technically termed as an allograft, as it is from a different person, but of
the same species, which in this case is a human being (Homo sapiens).
The total number of
organs transplanted annually worldwide is 135,860, of which 36,500 are carried
out in the US. This leaves behind approximately 730,000 patients in the US,
still in need of a life-saving organ transplant.
Out of the 36,500
organ transplants carried out annually in the US, approximately 7,000 are liver
transplants. Therefore, it is quite evident that there is a huge shortfall
of donor organs, including donor’s livers, in the US.
What are the Drawbacks of Current Methods of
The current method
used for preservation of human livers during transportation from donor to recipient,
keeps the liver viable for only around 9 hours. The donor’s liver is stored on
ice mixed with a preservative at a temperature between 4-8 ºC. After 9 hours,
however, the liver becomes irreparably damaged and
unsuitable for transplantation Freezing the liver below 0ºC
can preserve the organ longer, but freezing considerably damages the liver tissues,
making it unsuitable for transplantation purposes.
How Does the New Liver Preservation
Previous studies by
the same research group have shown that rat livers can be ‘super-cooled’ to
-6ºC without causing any tissue injury. This procedure prolongs the
preservation time of the rat livers from a matter to hours to a
matter of days. Importantly, the new technique has been hailed as an “awesome technology” by none other than
Dr. Francis Collins, MD, PhD, who is the Director of the National Institutes of
Health in Bethesda, Maryland, USA.
In this procedure,
prior to ‘super-cooling’, the donor’s liver is
conditioned to protect it from the sub-zero temperatures by perfusing it with a
preservative ‘cocktail’ using a special type of perfusion machine.
This perfusion ensures that the preservative is distributed evenly throughout
the liver tissue.
procedure, human donor livers can be transported at -4ºC
and revived at the time of transplantation by the machine perfusion technique using a slightly warm
perfusion fluid in order to bring out the livers from a state of suspended
“With ‘super-cooling’, as the volume increases it
becomes exponentially more difficult to prevent ice formation at sub-zero
temperatures,” de Vries says. “So
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
What are the Advantages of the New Liver
The major advantage
of the new liver preservation technology is that it significantly extends the
length of time that the donor livers can be kept out of the body during
transportation. This new technology has extended the out-of-body time for the
livers to 27 hours. This length of time is more than adequate to transport a donor liver anywhere across
the US, and possibly to other countries too.
In this regard,
Tessier says: “The extra time the technique can buy could make the difference between
success and failure of a liver transplant”.
concludes: “A lot of times when an organ
becomes available, there may not be a good match nearby, so in terms of
allocation, when you add that extra amount of time that means you can search a
wider distance which means you have a better chance of not only finding a good
match, but an excellent match.”
She adds: “And that means that you have less organ
discard, get more organs to recipients, and those organs are better
matched to the recipients, meaning that organ can have a longer life within the
Source of Funding
The study was
supported by the National Institutes of Health, the US Department of Defense
Health Program, the New England Donor Services, the Shriners Hospitals for
Children, as well as Sylvatica Biotech, Inc., and the Massachusetts General
Hospital Executive Committee on Research (ECOR) Program.
Source of Donor Livers
Donor livers for
this study were provided by the New England Donor Services, Waltham, Massachusetts
and LiveOnNY, New York City, NY, USA. Both of these are non-profit
- Supercooling Extends Preservation Time of Human Livers – (https://www.nature.com/articles/s41587-019-0223-y)