Spots as harbingers of rejection
Paul Werker: ‘We have been in contact with a brilliant surgeon from Oxford for several years. When we wanted to do the first an abdominal wall transplant in the Netherlands in 2015, he helped us in the preparation. For an intestinal transplant, we then also took a piece of the donor's abdominal wall. We did this to make more room for the bowel transplant. Just as an organ can be rejected, so can an abdominal wall. Our Oxford collegues saw from the abdominal wall that it showed spots when that happened. Often this was a precursor to rejection of the intestine. This allowed us to better monitor the condition of the transplanted intestine.'
Transplanting skin tissue
Paul Werker: ‘In Oxford, they got the idea to apply this principle differently. They took from a donor a piece of skin with blood vessels from the forearm, about 10 by 3 centimetres. In the recipient, the blood supply of that skin tissue can be properly connected to the circulatory system so that his or her blood flows through it. If spots or some kind of rash appear on that piece of skin, it is a sign that rejection is taking place in the skin and that this may be taking place in the transplanted organ as well. If you see earlier that this is likely to happen, you can intervene earlier. This can lead to less damage and rejection of the organ. Ultimately, this can lead to organs lasting longer and functioning better.'
First results in Oxford are good
Paul Werker: ‘They are currently doing a large study in Oxford on this in lung transplants. It has not yet been published, but initial results from a pilot are good. It seems almost too good to be true. We are the largest transplant centre in the Netherlands, so we thought ‘we're going to do that too.’
Skin also preserved in perfusion fluid?
Henri Leuvenink: ‘We immediately went one step further. In the UMCG, we developed the perfusion technique. In this, donor organs are preserved and even revived with a special, cold or warm oxygenated fluid. More and more organs go ‘on the pump’ first, as we call it. They also go on the pump for longer and longer periods of time. Only we don't know what happens to the skin tissue if we store it in the normal way, when it should be stored for the same length of time as the organs on the pump. Take a donor liver. That goes on the pump for twenty-four hours. Should we then put that skin tissue on the pump as well? Then they came to me to start investigating this, because in my lab we have a lot of experience with all kinds of perfusion set-ups.'
Right setup found in lab
Henri Leuvenink: ‘We have many different technologies in our lab, from very large to very small. From the slaughterhouse, we take organs from slaughtered animals. We put those organs on the pump in the lab in the same way as you would in the clinic. We have the right set-up for that. But nothing at all existed for this clinically yet. So the question was how to do that in the lab. I still had an old set-up in my lab, from the time we worked with rats. That turned out to have the right pumps to use for such small pieces of tissue. It turned out to work just fine. This allows us to treat both an organ and a loose piece of skin tissue well with perfusion fluid.'
Research into quality preserved skin tissue can start
Floris Kroezen: ‘The set-up to test the skin tissue in the lab is now ready. Now we can start researching the quality of this tissue after it has been preserved. I will soon join the Independent Collection Team to collect the skin tissues from donors. Thanks to a special method Paul Werker taught me, this can now be done in half an hour.'
‘Telltale signalling that light is on’
Floris Kroezen: ‘The skin tissue can be compared to one of those tell-tale signs downstairs that the light in the attic is on. The rejection of the organ can be compared to the light in the attic. The difference here is that the tell-tale signs that the light in the attic is going to turn on. You know before there is damage to the organ. You can then react very quickly'.
Talking to donor organ recipients
Floris Kroezen: ‘We also talk to people who are currently high on the waiting list. We need to know how they would feel about getting a piece of skin from a donor. We need to be well aware of that step. Because if the recipient does not like it, then you are nowhere.
Major benefits for patients
Floris Kroezen: ‘If this turns out to work, the benefits for a patient are huge. Suppose someone has had a heart transplant. According to protocol, they have to have a biopsy taken from the transplanted heart 17 times in the first year. That is being admitted every time, with a needle in the heart to take a biopsy and waiting for the results. And that 17 times! That causes a lot of tension in patients.'
Entirely new research for the Netherlands
Paul Werker: ‘I don't think we need to do very many transplants combined with pieces of skin to be able to say whether it works. Oxford has already done that. But this is still so new for the Netherlands, everything is still open. The ultimate goal is to apply this as standard in patient care, but that will take some time.'