‘Super Cool’ Way of Preserving Donor Livers

New technology developed can keep the donor’s liver safe and viable to more than three times that of standard preservation methods, reveals a new study. ‘Super-cool’ technology helps cool donor livers to temperatures below 0ºC without freezing the liver tissue. This will increase the availability of healthy livers for transplantation, improve utilization of the donor’s livers, as well as reduce the time constraints faced by the teams involved in procuring and transporting the donor livers.

The study was conducted by a team of researchers at the Massachusetts General Hospital, Boston, MA, USA and the research findings have been published in the journal Nature Biotechnology.

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Study Team

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.

Other team 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.

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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.

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What are the Drawbacks of Current Methods of Liver Preservation?

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 Technology Work?

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 of 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.

Using this 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 animation.

“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 Preservation Technology?

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”.

Concluding Remarks

Tessier 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 recipient.”

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 organizations.

Reference:

1. Supercooling Extends Preservation Time of Human Livers - (https://www.nature.com/articles/s41587-019-0223-y)

Source-Medindia