New machine can preserve donor livers for 1 week

Researchers in Switzerland have built a perfusion machine that can preserve human livers for transplantation for a week or more, potentially slashing the number of donor livers that must be discarded due to time-related deterioration.

Existing perfusion technology can preserve a donor liver for up to 24 hours.

The team of surgeons, biologists and engineers at University Hospital Zurich said their liver perfusion machine integrates core physiological functions, including automated glucose and oxygen management, waste-product removal and hematocrit control. The research is part of the Wyss Zurich “Liver4Life” project, and the study was published in the journal Nature Biotechnology.

The machine continuously moves the liver in an effort to mimic diaphragm oscillations. It is also fully automated, obviating the need for constant presence of personnel. The researchers first tested the machine on pig livers, then on 10 severely injured human livers that had been rejected by all European transplant centers, according to the study. After a seven-day perfusion, six of the human livers were producing bile, synthesizing coagulation factors, maintaining cellular energy and remained intact. They even healed from injuries and inflammation that occurred before or at the beginning of the perfusion process, the study said.

The researchers posited that such long-term perfusion may one day enable:

        Repair of severely fatty livers.
        Lowered odds of organ rejection.
        Chemotherapy that would be too toxic for the rest of a patient’s body.
        Long-distance transportation of organs to improve worldwide organ-sharing and transplantation logistics.
        Liver regeneration, with a donor liver split into several anatomic segments to regrow in the machine.

“Recent surgical procedures have shown that massive liver regeneration in humans can occur within 6 (days) of major tissue loss,” the researchers wrote. “If feasible, such an approach could double or even triple the availability of organs for transplantation. We may also imagine the use of partial grafts for auto-transplantation in patients with liver cancer, obviating the need for immune suppression.

“With further testing to demonstrate its use with injured livers and long-term transplantation success, this machine may provide an avenue for providing more patients with liver grafts,” they concluded.

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This Could Impair The Immune System

Researchers have now discovered how the fungus -- Aspergillus fumigatus -- knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

While, healthy people usually have no problem if microorganisms find their way into their bodies as their immune defence system will put the spores out of action, a specific type of fungus can threaten lives with a compromised immune system, such as AIDS patients or who are immunosuppressed following an organ transplantation, says a new study.

Researchers have now discovered how the fungus -- Aspergillus fumigatus -- knocks out the immune defences, enabling a potentially fatal fungal infection to develop.

Among other factors, it is gliotoxin -- a potent mycotoxin -- that is responsible for the pathogenicity of Aspergillus fumigatus.

Pathogenicity refers to the ability of an organism to cause disease.

"It was known that this substance has an immunosuppressive effect, which means that it weakens the activity of cells of the immune defence system. However, it had not been clear previously how exactly this happens," said a Professor.

To achieve this, they brought immune cells into contact with synthetically produced gliotoxin. These cells -- neutrophilic granulocytes -- represent the first line of the immune defence system.

Their task is to detect pathogens and eliminate them. As soon as such a cell comes into contact with a pathogen, for example a fungus, it releases specific messenger substances (leukotrienes) into the blood, which attract other immune cells. Once a sufficiently large number of immune cells has gathered, they can render the intruder harmless, findings showed.

This does not happen if the pathogen Aspergillus fumigatus is involved. Gliotoxin ensures that production of the messenger substance leukotrieneB4 in the neutrophilic granulocytes is inhibited, so that they are unable to send a signal to other immune cells. This is caused by a specific enzyme (LTA4 hydrolase) being switched off by the mycotoxin.

"This interrupts communication between the immune cells and destroys the defence mechanism. As a result, it is easy for spores - in this case the fungus - that enter the organism to infiltrate tissues or organs," said the Prof.
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