This work might improve the management of patients awaiting liver transplants, and eventually, other organs.
To benefit from an organ transplant, finding a compatible donor is not enough. It is also necessary to be able to carry out the transplant as soon as possible, otherwise a precious organ that might save a life might be lost. The deadlines are therefore extremely tight.
To slow cell death, the organ is placed in a refrigerated compartment; this greatly extends the length of time it remains viable. But following several hours, the ice crystals usually begin to damage tissue; the time that elapses between the death of the donor and the transplant should be a few hours at most.
The exact duration of this window depends on the organ in question. For some, like the heart, it only lasts 3 to 4 hours. Others are a little more permissive; the liver can for example be transplanted 24 hours following removal. But in any case, this generates a real logistical headache.
Preserving organs without ice
And above all, this has the effect of depriving a recipient of a potentially compatible organ, but located too far away to be transplanted on time. A situation that weighs heavily in terms of public health; today, the lack of available organs remains by far the main factor preventing many patients from having recourse to an often life-saving transplant.
For these reasons, many researchers are trying to develop techniques that might allow organs to be preserved for a much longer period of time. And this is precisely what the team of Pierre-Alain Clavien, surgeon at the University Hospital of Zurich, succeeded in doing.
To preserve the liver longer than usual, they used a technique called “perfusion normothermique ex situ”. The name may sound barbaric, but the concept is quite intuitive. Instead of stuffing the organ in an enclave full of dangerous ice for the cells, it is placed in a sterile environment maintained at 37°C, which is the ambient temperature of the human body – hence the term “normothermic”.
A more comfortable shelf life
A fluid charged with physiologically important elements such as nutrients and hormones is then circulated through it. And this approach works pretty damn well; in 2020, a other research team from Zurich showed that she was able to sustain a living human liver outside the body for 7 days with this technique.
But there is obviously a huge gap between keeping a bunch of cells alive and allowing a whole organ to play its role normally. It therefore remained to verify the relevance of this technique in real conditions. This is how, in May 2021, they found a donor who allowed them to test their protocol on a real patient.
They collected a partial liver from a 29-year-old woman who suffered from numerous abdominal tumors and a severe generalized infection. The organ therefore had to be thoroughly cleaned to ensure its viability before the transplant. However, this is an operation that is more or less incompatible with the time constraints associated with this procedure. In normal times, this organ would therefore have a good chance of being designated unusable.
A still resounding success one year following the transplant
But the normothermic infusion gave them plenty of time to do a deep graft clean for three days. On the morning of the fourth day, they carried out this experimental transplant on a doomed patient, suffering from advanced cirrhosis and recurrent liver cancer. And the experiment was a resounding success.
After a year of close follow-up, the graft took perfectly and the recipient is doing like a charm. No transplant rejection, loss of function or even damage to the bile ducts, although they are very common in liver transplants. The researchers even explain that the results are comparable to those of the most optimal transplant scenario, where a graft is taken from a living donor and transplanted directly into the recipient.
To have been able to preserve the organ for so long before the transplant is very exciting for clinicians. “This might open new horizons in the treatment of many liver diseases”, explain the researchers in their article. And the most interesting thing is that this concept, however imagined a long time ago, is still in its infancy; Over time, this approach is likely to continue to evolve towards ever-longer retention times for an ever-wider range of organs. Logistics that may better meet demand while waiting for in vitro cultures of personalized grafts to arrive on the market.
The text of the study is available ici.
