Supercooling "makes organs last longer

Researchers conserve human livers for the first time for 27 hours at minus temperatures

In the future, donor organs could be frozen for transport - and thus survive longer. © Sturti / istock
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Extremely cool: Researchers have succeeded for the first time in preserving human donor organs at sub-zero temperatures. They cooled livers down to minus four degrees Celsius without the tissue freezing. Through this so-called supercooling, the livers survived up to 27 hours outside the body. This is three times longer than is usually possible with common procedures, as the team reports in the journal "Nature Biotechnology".

For people with acute organ failure or a serious chronic illness, organ transplantation is often the last hope for recovery. But donor organs are scarce: In addition to the low number of organ donations also the time factor limits the supply. For example, extracted livers, kidneys and Co must be on average within nine hours at the recipient. Because outside the body, the sensitive cells and structures break down very quickly.

Researchers have therefore been looking for alternatives to the usual transport at four degrees Celsius in the cool box, which could prolong the survival of the organs. The focus has recently been on so-called supercooling. In this method, the organs are cooled down to minus temperatures, without causing the tissue to form harmful ice crystals. Inspired is the principle of nature: Even some animals can survive the cold season thanks to such a trick.

In the perfusion machine, the livers are treated in a similar way as in a bloodstream and purged with the antifreeze cocktail. Massachusetts General Hospital

Antifreeze cocktail for livers

But how does this succeed in organs? Five years ago, a team of US scientists showed that rat livers can be cooled to minus six degrees without freezing. This was made possible by the addition of special antifreeze agents. On the 200 times larger human organs, however, this procedure is not so easy to transfer. "The larger the volume, the harder it is to prevent the formation of ice crystals in sub-zero temperatures, " explains Reinier de Vries of Harvard Medical School in Boston.

But he and his colleagues have succeeded in doing just that: they have successfully used the supercooling method for the first time on human livers. To achieve their goal, the researchers adapted the method previously tested in rats on several points. First, they optimized the composition of the antifreeze solution: In addition to the antifreeze 3-O-methyl-D-glucose and a polyethylene glycol, they added trehalose and glycerol to the mixture. Together, these substances protect and stabilize the cells and prevent the formation of ice. display

Slowly cooled down

For the decisive step, the researchers coupled human livers to a perfusion machine that supplies the organs with oxygen and nutrients, much like an artificial bloodstream. With this machine, they gradually fed in the preservative fluid, which was distributed evenly throughout the organ.

The liver was then cooled slowly to minus four degrees Celsius. The team made sure that there was no contact with air. Because they had discovered that interactions with air increase the risk of spontaneous crystal formation on the organ surface. After preservation, the livers were gradually returned to room temperature via the perfusion machine.

Thawed and functional

How well had the organs survived the procedure? The results showed that thanks to the supercooling method, the livers survived up to 27 hours out of the body - three times longer than in the conventional cool box usual. As the scientists report, the function of the livers after the hypothermia procedure was as good as before. Although they have not transplanted the organs. However, simulations suggested that livers would probably easily survive transplanting into a new body.

If further studies confirm the utility of the new method, valuable time would be gained: "When an organ becomes available, a suitable recipient is not always close, " explains Dert de Vries' colleague Shannon Tessier. "Longer shelf life means more time to find a suitable patient and transport. And that means fewer donor organs need to be disposed of, and more patients will receive well-suited organs to live with for a long time. "

Other alternatives in the test

However, the supercooling process is not the only method currently being discussed as an alternative to the cooler. For example, physicians also experiment with procedures whereby organs are not cooled but held in a state such as in the body. At the same time organs during transport practically pretend to be in an organism. This technique could be particularly useful for previously damaged organs, which are often less able to withstand cooling processes. (Nature Biotechnology, 2019; doi: 10.1038 / s41587-019-0223-y)

Source: Harvard Medical School / National Institute of Biomedical Imaging & Bioengineering / Massachusetts General Hospital

- Daniel Albat