A new method for supercooling human donor livers to subzero Celcius temperatures without freezing can triple the time that a donor organ stays safe and viable during transportation from the donor to the recipient.
This development could greatly expand the availability of healthy livers for transplantation, improve organ utilization, and reduce some of the time pressure on procurement and transplantation teams.
This breakthrough addresses a dire need: Because of the current donor organ shortage, only about 36,500 of the 730,000 patients with fatal end-stage organ disease receive a life-saving organ transplant each year in the U.S.
The technique, developed by Harvard Medical School investigators based at the Center for Engineering in Medicine at Massachusetts General Hospital, is described in Nature Biotechnology on Sept. 9. The team at Mass General was led by Reiner de Vries, HMS research fellow in surgery, Shannon Tessier, HMS instructor in surgery, and M. Korkut Uygun, HMS associate professor of surgery.
Currently, a donor human liver is kept only about nine hours outside the body—stored on ice in a preservative solution at temperatures ranging from 4 to 8 degrees Celcius (39.2 to 46.4 degrees Fahrenheit)—before the tissues become irreparably damaged and the organ has to be discarded.
At colder, subzero temperatures the organ would survive longer, however, freezing causes serious damage. This is similar to the damage deep frostbite can cause to skin and extremities and would make the organ not transplantable.
But as the research team previously demonstrated with rat livers, it is possible to “supercool” them to -6 C (21.2 F) without causing injury to the tissues, extending their preservation time from a matter of hours to more than a day. The technique was hailed as one of several “awesome biomedical technologies” by National Institutes of Health Director Francis Collins in his Director’s Blog.
“With supercooling, as the volume increases, it becomes exponentially more difficult to prevent ice formation at subzero temperatures,” de Vries said. “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.”
Prior to supercooling, the livers are conditioned to protect them from the cold with a preservative solution that is delivered via machine perfusion, another technique already in use to improve organs for transplantation. The perfusion ensures that the preservative solution is evenly distributed throughout the organ.
The human livers can then be transported at -4 C (24.8 F). At the transplantation site, machine perfusion is again used to carefully warm the livers and bring them out of their state of suspended animation.
Using this technique, the investigators have been able to extend the out-of-body time for livers to 27 hours—long enough for a donated organ to be shipped virtually anywhere in the United States or beyond.
The extra time the technique can buy could make the difference between success and failure of a liver transplant, Tessier said.
“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 said. “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 recipient.
The study was supported by the National Institutes of Health, the Department of Defense Health Program, New England Donor Services, Shriners Hospitals for Children, and Sylvatica Biotech. Continuation of the studies is funded by the Mass General Executive Committee on Research program. Donor organs for this study were provided by New England Donor Services and LiveOnNY, and the authors express their gratitude to the donors and their relatives for enabling this research with their gifts.
Adapted from a Mass General news release.