July 21, 2014

Preserving Livers for Transplantation

At a Glance

  • A new technique increased the time that rat livers can remain viable outside the body.
  • If the approach succeeds in humans, it could aid organ transplant efforts.
Rat liver in a small dish. A supercooled rat liver in the machine perfusion system.Wally Reeves, Korkut Uygun, Maish Yarmush, Harvard University

Due to a shortage of donor organs—including kidneys, hearts, lungs, corneas, and livers—more than 120,000 patients nationwide are currently on waitlists for organ transplantation. For severe liver failure, liver transplantation is the only available treatment, but there aren’t enough donors to fill the need.

Extending the time organs can survive outside the body would allow organs to be transported across greater distances. It would also improve safety by increasing time for preparation and planning. The long-term preservation of human organs, however, is challenging. Organs have multiple cell types and structures that react differently to temperatures below freezing. Livers can currently be preserved outside the body for up to 24 hours using ice-cold temperatures and a special chemical solution developed by NIH-funded scientists at the University of Wisconsin-Madison in 1983.

Drs. Martin Yarmush and Korkut Uygun at Massachusetts General Hospital aimed to develop a way to preserve organs for longer periods. Their work was supported by NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The technique they developed was described in the July 2014 issue of Nature Medicine.

The team used a machine perfusion system to preserve rat livers. This system maintained a gentle flow of cooled, nutrient- and oxygen-rich solution around the livers. To protect the organs from cold damage, the team added a nontoxic sugar compound called 3-O-methyl-D-glucose (3-OMG). This compound can enter liver cells but can’t be metabolized, allowing it to act as a protectant against the cold. The team also added polyethylene glycol (PEG) to the solution during a supercooling stage, when temperatures were lowered to −6 °C, or 21 °F. PEG, which is related to the active ingredient in antifreeze, prevents freezing and protects cell membranes at low temperatures.

The livers were cooled and stored for several days, then rewarmed in the machine perfusion system and transplanted into healthy rats. All the rats that received supercooled livers stored for 3 days were alive 3 months later. The survival rate for animals receiving livers that had been stored for 4 days was 58%. None of the rats who had transplants using current methods survived.

“The longer we are able to store donated organs, the better the chance the patient will find the best match possible, with both doctors and patients fully prepared for surgery,” says Dr. Rosemarie Hunziker, director of NIBIB’s tissue engineering and regenerative medicine program. “This is a critically important step in advancing the practice of organ storage for transplantation.”

This approach must undergo extensive testing and refinement before use in people. The next step will be to conduct similar studies in larger animals.

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References: Supercooling enables long-term transplantation survival following 4 days of liver preservation. Berendsen TA, Bruinsma BG, Puts CF, Saeidi N, Usta OB, Uygun BE, Izamis ML, Toner M, Yarmush ML, Uygun K. Nat Med. 2014 Jul;20(7):790-3. doi: 10.1038/nm.3588. Epub 2014 Jun 29. PMID: 24973919.

Funding: NIH’s National Institute of Biomedical Imaging and Bioengineering (NIBIB) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).