I am face to face with a freshly removed pig鈥檚 liver connected to a maze of tubing and sitting in a clear plastic tub. It isn鈥檛 looking healthy 鈥� it is dull with a greyish-brown complexion. But then I am given permission to press a button and the equipment whirs into life.
The device effectively performs the function of a heart and lungs, and was developed by Peter Friend and his colleagues at the University of Oxford and their spin-out firm . It perfuses the liver with oxygenated blood warmed to body temperature, and the organ quickly starts to flush a dark reddy-brown and look glossier, even plumper.
These kinds of machines were invented to keep people alive while their heart was stopped for surgery, but smaller versions are now used to keep organs alive outside the body to aid in transplant operations. Such devices are now used in a few heart, liver and kidney transplants, both to extend the time an organ can remain safely out of the body and to help doctors judge if an organ is functioning well. 鈥淚t鈥檚 like taking it for a test drive,鈥� says Constantin Coussios of OrganOx.
Advertisement
But the researchers want to go further and start using this ability to keep an organ alive outside the body to manipulate it, and even heal it from disease.
Fatty liver disease
Their first goal is to tackle an increasingly common problem, fatty liver disease. This occurs when the organ鈥檚 cells accumulate too much fat. Although it can happen in people who are slim, it is more common in those who are overweight, affecting nine out of 10 people who are obese.
Depending on the disease鈥檚 severity, transplanted fatty livers don鈥檛 function as well as transplants of livers in good shape. With waistlines expanding, that means increasing numbers of donated livers have to be turned down. Fatty liver is the explanation for half of all livers rejected for transplant in the UK.
But what if we could get a liver to lose its fat while it is kept outside the body? Friend and his team have developed a way to do this, effectively putting an isolated liver on a crash diet for two days.
They achieve this using two chemicals that make cells release fat, and then filter out fat particles from the blood used to keep a liver alive. The chemicals, forskolin and L-carnitine, are commonly sold as weight loss supplements.
In 2018, the team showed that the approach makes livers lose fat, in a study that but had been turned down due to their fattiness. The researchers鈥� next step is to repeat the 鈥渄e-fatting鈥� method, this time with livers that have only borderline fat levels and are destined to go into people.
Out-of-body treatment
They hope to start the trial at the end of this year. 鈥淭o my knowledge, it would be the first time a human organ has been treated for any disease while outside the body,鈥� says Friend.
Other groups are trying different approaches. Robert Porte at the University of Groningen, in the Netherlands, and his colleagues, for example, are going to try heating livers to 40掳C, to raise their metabolic rate and make them burn more fat. 鈥淚t would be like causing a fever,鈥� says Porte.
Fatty liver isn鈥檛 the only condition that could be treated outside the body. While an organ is isolated in this way, it may also be possible to dose it with cell or gene therapies that make it less prone to sparking an immune response in the recipient. Transplant recipients currently have to take immune-suppressing drugs for the rest of their lives, leaving them prone to infections and cancer.
Friend would also like to try hooking up livers with cancer to his machine while they are still inside the body. The idea is that, by temporarily disconnecting them聽from the body鈥檚 blood supply, it might be possible to deliver higher doses of chemotherapy, without causing serious side effects elsewhere.
Sign up to our free Health Check newsletter for a round-up of all the health and fitness news you need to know, every Saturday
