Researchers Develop “Supercool” Organ Preservation Technique to Give Clinicians and Recipients More Time for Transplants

Liver undergoing machine perfusion

If you have ever watched a hospital drama TV series, you have probably seen an episode where the cast is racing against the clock to transplant an organ. While certain aspects of the show may be dramatized, the time crunch for an organ transplant is very real.

One of the most pressing concerns is making sure the organ is preserved outside the human body. Keeping an organ viable during transport is difficult because it has to be cool enough to prevent the tissue from breaking down, but cannot be so cold that it freezes and develops an ice injury.

Currently, most donated organs are transported in coolers on ice, and at best those organs can last anywhere from four to twelve hours. But a lot has to happen in that time window in order for the transplant be a success.

Doctors have been trying for decades to figure out a way to give these organs and the transplant teams more time, and it looks like one Mass General team has just made it possible.

For the first time, researchers successfully “supercooled” a human liver and returned it back to normal body temperatures without any ice injury. Using this supercooling preservation method, the research team, led by Reinier de Vries, MD, were able to triple the shelf-life of human livers from about nine hours to 27 hours.

The Current State of Organ Transplants

When a donor becomes available, transplant teams feverishly work to coordinate transportation logistics, which are often very complicated. Since donor livers are generally only viable for about nine hours, coordinating efforts puts extreme stress on the transplant team and the recipient, leaving very little time to prep.

Matching the patient to the best donor can also be a challenge.

When a recipient goes on the transplant list there are a number of factors that are considered to find the best match, such as body size, blood type, condition severity and distance. But, depending on the situation, certain factors become more important. “This can sometimes result in an individual receiving a good match, but maybe not the perfect match,” says de Vries.

If organs could be preserved for longer periods of time, it could result in more people receiving their perfect matches, an increased lifetime of the organ after transplantation and fewer organs being discarded when time runs out.

How Donor Organs Become “Supercool”

Supercooling is the process of cooling something to subzero temperatures without the formation of ice crystals, and while it sounds counterintuitive, it is possible.

Most water freezes below 32 degrees, but that is in part due to its interaction with other external factors, says de Vries. When cold water interacts with air, certain proteins and other impurities it can aid in the fixation of the freely moving water molecules to form ice. But pure water on its own can remain in liquid form below the freezing point in small volumes.

So how did researchers take the largest solid organ in the human body, made mostly of water, and supercool it without any damage?

In most cases, before transporting an organ it is flushed with a cleansing and preservative solution using an IV. While this flush gets the job done, it can result in uneven solution distribution and limited protection, says de Vries. Instead, the research team used machine profusion—a pressure-controlled pump that can provide a steady and even circulation of solution throughout the liver.

Even if the organ is fully flushed, there can still be a risk of freezing given the tissue still contains a lot of water. To enhance the organ’s freeze-resistance the team also incorporated higher levels trehalose and glycerol—two naturally-occurring sugar molecules—into the solution. At higher levels, these molecules work as the body’s natural version of antifreeze.

Finally, before putting the liver into a chiller that circulates a special freeze-resistant solution, the team placed the organ in a plastic bag with a small amount of solution and removed all of the air bubbles, like a vacuum seal.

These three steps allowed the research team to triple the preservation time from nine to 27 hours without tissue damage.

How Supercooling Can Be Used in the Future

Supercooling can become challenging as the size of the transplanted organ increases, but since DeVries and his team managed to succeed with the liver, the largest solid organ in the human body, they are confident they can apply this technique to other donor organs.

They are currently exploring various protocols for supercooling organs like kidneys, ovaries and hearts, but also larger transplants like limbs for those who have from suffered traumatic injuries.

The next step is to conduct more trials using laboratory models to monitor post-operation health and progress and ensure that this technique is safe for humans before moving on to clinical trials. If this technique is found to be safe, it could help preserve countless organs for longer periods of time and save numerous lives.

“There is just such a big need, and transplantation is a race against the clock, so if we have more time available it could really improve transplant outcomes.”

Reinier de Vries, MD

About the Mass General Research Institute
Massachusetts General Hospital is home to the largest hospital-based research program in the United States. Our researchers work side-by-side with physicians to develop innovative new ways to diagnose, treat and prevent disease.
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