At normal temperature
Human liver learned to store for a week without freezing
Polina Loseva, N+1
Swiss scientists have developed a system that allows you to store an isolated liver for a week. At the same time, the liver retains its basic functions and is not destroyed. To achieve this effect, the researchers had to carefully select the composition of the blood for washing, as well as simulate the work of the pancreas, liver and diaphragm. The method was tested not only on pig organs, but also on ten human organs, six of which successfully underwent the procedure. The work was published in the journal Nature Biotechnology (Eshmuminov et al., An integrated perfusion machine preserves injured human livers for 1 week).
On the left – an unfused liver, on the right – a liver treated with a new device. Drawing from the USZ World Premiere in Zurich press release: Machine Keeps Human Livers Alive for One Week Outside of the Body – VM.
Two approaches are currently competing in the field of storage of isolated organs. One suggests maintaining the liver at its natural body temperature by constantly washing it with a solution similar to blood in properties and composition (this process is called perfusion). The second one is based on cooling to a temperature of about zero degrees or lower, which should stop the decay processes inside the organ and ensure its safety.
So far, the second approach has had the palm. While the normothermic method allows the organ to be stored for an average of about 9 hours, with the help of supercooling, scientists have recently achieved liver survival even after 24-40 hours. However, this time may still not be enough to prepare the future liver host for surgery. In addition, in order to radically cool the liver, it has to be impregnated with cryoprotective substances, which theoretically can affect its work.
Therefore, a group of scientists led by Pierre-Alain Clavien from The University Hospital of Zurich decided to give a chance to the first, normothermal method. As part of the Liver4Life project, researchers have designed an improved perfusion system. Two blood vessels approach the isolated organ: the hepatic artery (the blood in which is enriched with oxygen) and the portal vein (which brings substances that have entered the blood in the intestine). In both vessels, the device monitors pressure, oxygen saturation level, glucose concentration and other nutrients, and blood cellular composition.
The device also simulates the activity of the pancreas, releasing insulin and glucagon into artificial blood, which should affect glucose metabolism in liver cells. In addition, the device has some kidney functions: the blood is constantly undergoing dialysis, maintaining constant osmotic pressure and being cleared of metabolic products. Finally, in some way, the device imitated the diaphragm: the isolated liver moved in the same way as it does in the human body with each inhalation and exhalation, which contributes to the blood supply to the tissue.
Before moving on to human experiments, the researchers tested their perfusion system on 70 pig organs. They confirmed that the liver is able to survive in isolation for about a week and does not lose its functions. In the experiment, the liver stored glucose in the form of glycogen, secreted bile and did not break down (judging by histological sections and markers of inflammation).
Scientists planted three of the test organs back into the pigs' bodies. Ethical standards allowed them to observe liver survival only for three hours, because after that the effect of anesthesia ended, and experiments on animal survival without anesthesia are prohibited by a local animal welfare organization. Nevertheless, three hours after the operation, those organs that were kept isolated for a week isolated as many markers of inflammation as the liver of short-term storage. So scientists have confirmed that no additional damage as a result of a week of life of the whole body in the organs did not occur.
Finally, the researchers were able to move on to experiments on human organs. They used ten organs that were unsuitable for transplantation for various reasons. The same perfusion system was used for them, however, it was necessary to adjust the composition of artificial blood so that it became similar to human blood. Six out of ten organs turned out to be viable: during the week of being in isolation, the number of pro-inflammatory markers and dying cells in them first increased, but then decreased. They continued to accumulate glycogen, absorb oxygen, produce bile and blood proteins, such as albumin, as well as purify the blood from lactic acid and nitrogenous metabolic products.
The authors of the work believe that the difference in the survival rate of donor organs may be due to the fact that they were initially not completely healthy – otherwise they would have been approved for transplantation. Nevertheless, the researchers expect that their method can one day be used to "resuscitate" such organs: in the week that is allotted for storage, they can theoretically be "cured" and grow to a more functional state.
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