Groningen researchers are trying to ‘refurbish’ donor organs as a solution to the growing organ shortage

The two pig kidneys were refrigerated for 24 hours and oxygenated. Now it’s time to hang them on the warm perfusion machine.

Anne van Kessel, for NEMO Kennislink

“I am now going to cut off a piece of the kidney,” says medical student Baran Ogurlu in the surgical laboratory of the UMC Groningen (UMCG). Two greyish pig kidneys lie on a tray lined with white gauze. The kidneys come from the slaughterhouse and would otherwise have been thrown away. “Yesterday morning I picked them up and rinsed them with a liquid of four degrees, so that the pig’s blood came out. I then connected them to these machines, which cool the kidneys to ten degrees and give them oxygen, the so-called cold perfusion.” He points to two styrofoam coolers with a pump in them. “They’ve been in there for exactly 24 hours now.” The cold inhibits the metabolism and therefore the organ remains good.

Ogurlu carefully cuts several pieces of the kidneys. His fellow student Isa van Tricht places them on a filter paper. A filter paper is placed on top of the biopsy, after which Van Tricht freezes the pieces in liquid nitrogen. Ogurlu: “With these pieces we do a number of analyzes to check whether the kidney is damaged.” They do this to see whether the next step improves the quality of the kidney.

For that next step, Ogurlu and Van Tricht couple the kidneys to two different perfusion machines. “One machine gradually warms up the kidney to 37 degrees. The other machine exposes the kidney directly to that temperature,” explains Ogurlu. Both machines are so-called normothermic perfusion machines: they keep the organ at the human body temperature.

Ogurlu and Van Tricht take biopsies of the two kidneys to examine the quality.

Anne van Kessel, for NEMO Kennislink

Research has shown that an abrupt increase in temperature and pressure can lead to organ damage. Ogurlu: “The idea is that if you do it gradually, it’s better for the kidney. I am now looking at how gradually you should do that and that is why I am testing three different heating rates. Today we’re doing one of those. Think of it as a warm-up of a top athlete. Does that warm-up make sense? And if so, what should it look like?”

Rejected Organs

The Dutch are getting older and fatter. This also increases the risk of diseases such as cancer, cardiovascular diseases and diabetes. These diseases and an aging population increase the chance that patients will one day need a donor organ. “Fifty years ago, most donor organs came from young men who had died in road accidents,” says transplant surgeon Cyril Moers. “Today, potential organ donors are older and as a result a third of the organs are rejected,” adds Professor of Experimental Transplantation Surgery Henri Leuvenink. A heart from an old patient is often rejected, as are organs from people who have been ill.

The question is whether that is right. In recent weeks, we at NEMO Kennislink described ways to solve the organ shortage, for example with the help of animal organs, or with the help of human organs that grow in animals. But according to the researchers at the UMCG, it can be simpler. According to them, much can be gained by looking more closely at which organs are suitable for transplantation and by refurbishing rejected organs.

“An organ is so precious,” says Moers. “It’s really close to my heart to have to disapprove of it.” That is why the people of Groningen are looking at whether they can make this assessment more objectively, because now a transplant surgeon makes this assessment visually. Moers: “This can be done, for example, by first hanging the organ on the perfusion machine and measuring how it performs. An organ from a 70-year-old with a healthy lifestyle can be better than an organ from a 50-year-old with a very unhealthy lifestyle.” The UMCG regularly receives rejected livers that other hospitals do not want. Sometimes, after a check on the perfusion machine, the organ is still suitable for transplantation. “Thanks to perfusion, we have already been able to transplant 40% more livers,” says Leuvenink.

If the rejected organs do not pass the extra test in the UMCG, there is no other option for the time being than to destroy them. The scientists hope to change that in the future. On the one hand, by making the inspection even more accurate: by placing the entire perfusion set-up in an MRI scanner, for example, the researchers can look inside the kidney and determine which parts are functioning well or less well. On the other hand, they want to use experiments to find out whether organs recover on the cold and/or warm perfusion machine. This too should ultimately lead to more donor organs. To find out, they are investigating how the slaughter organs of animals react to the different steps.

The kidney is on the warm perfusion machine. He really pees.

Anne van Kessel, for NEMO Kennislink

urinating organ

“Do you see the kidney turning pink yet?” Ogurlu asks in the lab. We’re looking at a kidney in a container of red liquid. “That’s artificial blood,” he explains. “In that way, the situation is most similar to that in the human body.” The kidney is connected with tubes to a pump, which pushes oxygen and nutrients through the organ and removes waste. “Look, he’s really peeing,” says Ogurlu, pointing to the liquid that ends up in a glass bottle through a tube. It looks like syrup. “Every hour we take samples of the blood and urine to determine kidney function.”

The devices that Ogurlu uses are very similar to the devices that are already used in the hospital. “By using the same devices in the lab as in the clinic, the research is very translational,” explains Leuvenink. This means that the results will soon be easy to apply in the operating room.

Extend storage time

Kidneys as well as hearts and livers are regularly coupled to perfusion machines. But it is not yet clear which form of perfusion will benefit the organs the most. In addition, the Groningen scientists are investigating whether it is useful to administer medication or stem cells during perfusion and whether they can defat livers that are too fatty.

That research is also happening in other places. Last year Swiss researchers showed that a new machine could keep human livers alive outside the body for up to a week, and improve the quality of the livers. The system they developed kept the liver at 34 degrees and continuously measured the blood sugar concentration. It also injected insulin or glucagon when needed. A dialysis unit filtered the waste products from the blood and a pump inflated a balloon under the liver fifteen times a minute, keeping the liver moving, just like in a body.

The perfusion machine that is used is very similar to the machine that doctors use in the hospital.

Anne van Kessel, for NEMO Kennislink

Perfusion can be useful not only to check or repair organs, but also to extend the storage time. In 2019, American scientists showed that super cooling can extend storage time up to 27 hours. A liver is kept below minus 4 degrees Celsius and then connected to a cold perfusion machine. “Because of this time gain, you can, for example, postpone an operation from the night to the morning,” says Moers. “Surgeons now often work at night. That has an impact on your health. Humans are not made to work at night.” In addition, it is useful if several organs become available at the same time, but there are insufficient operating rooms and operating teams.

Four hours after Ogurlu and Van Tricht have connected the kidneys to the machines, they are allowed to come off. The students take some more biopsies, to compare with the initial situation. And then it’s over. For the time being, they are conducting their research with slaughter organs. Van Tricht: “If this proves to work well, we want to continue with rejected human organs and eventually we hope to apply this to all donor organs.” Moers concludes: “Of course it would be great if this were successful. But we must not forget that we still have few organ donors. Few people are in the Donor Register with a ‘yes’. That’s the biggest problem. If everyone were registered with ‘yes’, this research would not be necessary.”


Source: Kennislink by www.nemokennislink.nl.

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