By using the active ingredient in antifreeze, researchers from Harvard University have developed a 'supercooling' technique that triples the length of time a rat's liver can be stored outside the body prior to transplantation. The technique, should it work on human organs, could revolutionize how transplants are done.
Since the advent of whole organ transplants some 60 years ago, physicians have been able to swap-out everything from kidneys, hearts, and lungs to corneas and skin. But due to the chronic shortage of donor organs, some 120,000 patients remain stuck on waiting lists in the US alone. Eventually, we'll be able to growour own organs, but until then, we'll have to do our best to preserve these organs outside the body.
Current technology lets us preserve livers outside the body for a maximum of 24 hours using a combination of cold temperatures and a chemical solution that keeps livers from dying while in transit to recipients. Extending this painfully short shelf-life would allow for more time to prepare patients for surgery and dramatically expand the limits of the geographic donation area.
But preserving organs in extreme cold temperatures is highly problematic. Once you get down to -320 degrees Fahrenheit — the temperature for cryopreservation — organs experience extensive tissue damage. The new technique, developed by Martin Yarmush and Korkut Uygun from the Center for Engineering in Medicine at Massachusetts General Hospital (MGH) in Boston overcomes these issues.
The National Institutes of Health, which provided support for the study, explains the four-step preservation process:
The first step is to employ the use of machine perfusion — a way of delivering oxygen and nutrients to capillaries in biological tissues while outside the body — to supercool the liver tissue without causing irreversible damage to the cells. In order to accomplish this, the MGH team added 3-OMG (3-O-methyl-D-glucose), a non-toxic, modified glucose compound, to the solution being delivered to the liver. The 3-OMG is taken up and because it cannot be metabolized by cells, accumulates in the hepatocytes (liver cells), acting as a protectant against the cold. The team also modified the solution by adding PEG-35kD (polyethylene glycol) to specifically protect cell membranes. Ethylene glycol is the active ingredient in anti-freeze, and it works by lowering the freezing point of a solution.
The livers were then slowly cooled below the freezing point, to 21 degrees Fahrenheit, without inducing freezing — thereby supercooling the organ for preservation. After storing the organs for several days, the researchers again used machine perfusion to rewarm the organ, while also delivering oxygen and other nutrients to prepare the organ for transplantation.
Using this new technique, the researchers were able to store the supercooled rat livers for three days (72 hours) and four days (96 hours) at 21 degrees Fahrenheit. All the rats who had supercooled livers stored for three days survived three months, but none of the rats who had transplants using current methods did. The survival rate for animals receiving livers stored for four days was 58 percent. 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.
Amazing. The researchers kept the organ in supercooled storage for nearly four days — a length of time that puts virtually every part of the world within reach.
But as bioethicist Arthur Caplan points out, there's also a dark side:
The next step will be to conduct similar studies in larger animals and with different organs.
Read the entire study at Nature Medicine: "Supercooling enables long-term transplantation survival following 4 days of liver preservation". Additional information via NIH.
Image: Wally Reeves, Korkut Uygun, Maish Yarmush, Harvard University