Supercooling Extends Liver Preservation for Transplantation

A new preservation technique dramatically increases the amount of time organs could remain viable outside of the body.

Developed by researchers at Massachusetts General Hospital (MGH; Boston, USA), the preservation technique has tripled the amount of time that rat livers can be stored before transplantation. The first step involves perfusion of the liver to supercool the tissue without causing irreversible damage to the cells using 3-O-methyl-D-glucose (3-OMG), a nontoxic, modified glucose compound that acts as a protectant against the cold. The solution also includes polyethylene glycol (PEG-35kD, the active ingredient in antifreeze), to specifically protect cell membranes and lower the freezing point of a solution.

The rat livers were then slowly cooled further to below freezing point, reaching -6 °C without inducing freezing, thereby maintaining organ suitable for preservation. Using this new technique, the researchers were able to store the supercooled rat livers for up to 96 hours. After storing the organs for up to four days, the researchers again used machine perfusion to rewarm the organ, while also delivering oxygen and other nutrients to prepare it for transplantation.

All the rats who were implanted with the supercooled livers stored for three days survived three months; the survival rate for animals receiving livers stored for four days was 58%. When testing to see if all the steps in their method were essential, the researchers found that if they eliminated the supplemental components PEG-35kD or 3-OMG, none of the rats survived for even a week. If they did not use machine perfusion or supercooling, death occurred within an hour of transplantation. The study was published online on June 29, 2014, in Nature Medicine.

“We have shown that each of these components is individually required to achieve viable supercooling preservation in our model, as evidenced by long-term recipient survival,” concluded lead author Martin Yarmush, MD, PhD, and colleagues. “To our knowledge, supercooling is the first preservation technique capable of rendering livers transplantable after four days of storage. As extensive screening of different additives or variations in protocol is still ongoing, additional improvements could be achieved from future experimentation.”

Current technology can preserve livers outside the body for a maximum of 24 hours using a combination of cold temperatures and a chemical solution developed by scientists at the University of Wisconsin-Madison in 1983. The solution helps keep the liver tissue from dying while in transit to the recipient site. The difficulty with long-term preservation of human organs stems mostly from the extensive tissue damage that occurs when organs are frozen. While successful for single cells and simple tissues, the problem is exacerbated with whole organs because of the multiple cell types and other structures that react differently to cold.

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