Monday 30 June 2014 – 8am PST
In the US alone, around 18 people die every day waiting for transplants that are unable to take place due to a shortage of donated organs. But a new study funded by the National Institutes of Health details a new supercooling method that could preserve donor livers for 3-4 days, potentially transforming organ transplantation on a global scale.
The research team, including investigators from the Center for Engineering in Medicine at Massachusetts General Hospital and Harvard Medical School in Boston, MA, recently published their findings in the journal Nature Medicine.
According to the researchers, current preservation techniques can store a donor liver outside the human body for up to 24 hours. This involves a combination of a chemical solution – which stops tissue damage – and cold temperatures.
But there is no doubt that being able to preserve organs for a longer duration would not only help to tackle the problem of donor organ shortages – allowing organs to be distributed to destinations further away – but it would allow more time to find better organ matches for recipients, potentially improving transplantation outcomes.
However, the researchers note that long-term human organ preservation has been challenging. Cryopreservation – freezing an organ at -320.8 degrees Fahrenheit – is used for single cells and simple tissues. But for whole organs, the team says the process can cause severe tissue damage and make the organ unsuitable for transplantation.
In this latest study, funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) – both a part of the National Institutes of Health – the researchers set out to find a solution.
Four-step technique ‘preserved rat livers for 3-4 days’ The team created a four-step preservation technique using existing technology, which they tested on the livers of rats. This involved the use of machine perfusion, two anti-freeze compounds and a supercooling method.
Supercooling machine The team created a four-step preservation technique that successfully stored rat livers for 3-4 days. This involved the use of machine perfusion, two anti-freeze compounds and a supercooling method. Image credit: Wally Reeves, Korkut Uygun, Maish Yarmush, Harvard University Machine perfusion – a method that delivers nutrients and oxygen to capillaries in organs while they are outside the body – allowed them to supercool the liver while avoiding tissue damage.
They did this by adding a nontoxic modified glucose compound – called 3-O-methyl-D-glucose (3-OMG) – to a solution that was deposited into the liver. The researchers explain that 3-OMG accumulates in the liver cells and protects the liver against cold temperatures. The team also added polyethylene glycol (PEG-35kD) to the liver solution, which lowers the freezing point of a solution and protects the cell membranes.
The researchers then slowly cooled the livers to below the freezing point (21 degrees Fahrenheit) without actually freezing them. Using this method, they were able to store some of the rat livers for 3 days, while others were stored for 4 days.
Machine perfusion was used again to warm the rat livers while delivering nutrients and oxygen to the organs, making them ready for donation.
After transplanting the donor livers into rat recipients, they found that the rats that received the 3-day preserved livers survived 3 months, while other rats that received livers preserved using current methods did not survive. Rats that received livers preserved for 4 days had a 58% survival rate.
The team notes that when they removed PEG-35kD or 3-OMG from the liver solution, the rats survived for less than a week, while lack of machine perfusion or supercooling triggered death within 1 hour of transplantation.
Commenting on the findings, Rosmarie Hunziker, PhD, program director of tissue engineering and regenerative medicine at the NIBIB, who was not involved in the study, says:
“It is exciting to see such an achievement in small animals, by recombining and optimizing existing technology. The main point here is that using all of these approaches at once was what led to success. Halfway measures did not do. Such a tour de force reflects this team’s very deep understanding of the complex processes at work here, and how they relate simultaneously to each other.”
The researchers say they now plan to carry out similar studies in larger animals, noting that the technique needs to undergo extensive testing and clarification before it can be considered for human use.
However, they believe their research demonstrates the potential for 3- and 4-day organ storage, which could transform the future of transplantation.
“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 Hunziker. “This is a critically important step in advancing the practice of organ storage for transplantation.”
Late last year, Medical News Today reported on a study by researchers from the University of Florida, which investigated the use of pig kidneys for human transplantation.
Written by Honor Whiteman