Every day, people wait for a donor organ that could save their lives. But the time an organ can remain viable outside the body is limited. The PhD research of Irina Filz von Reiterdank shows that donor organs can be preserved for longer and even improved before transplantation. She developed the first reproducible method for genetically modifying entire donor organs. Her work brings a new vision of transplant medicine closer: Preserve, Edit, Transplant.
Today, organ transplantation is largely about keeping donor organs in the best possible condition until they can be transplanted. Irina Filz von Reiterdank believes there is potential to do more: “What if we could not only preserve organs for longer, but also improve them before they are transplanted?” More time and targeted modifications could make more donor organs suitable for transplantation and lead to better, more personalised care for patients.
To make this possible, Irina uses machine perfusion: a technique in which a donor organ is connected to a machine outside the body that supplies it with oxygen and nutrients. This keeps the organ in good condition for longer and creates time to examine or even treat it.
“We can create organs that respond to their environment, detect rejection at an earlier stage, or treat themselves locally. We call these smart organs: donor organs that gain new properties before transplantation.” In the future, this could reduce patients’ risk of rejection and make them less dependent on drugs that suppress the immune system.
Irina succeeded in making lasting genetic changes to entire organs, and was the first to describe in detail how to do this reliably. This was far from easy: “It took a year and a half before the genetic modification of organs worked. Many experiments did not produce the desired results, but each time we learned something that brought us one step further.”
“Genetic modification of individual cells in a dish has been possible for some time. A complete, functioning organ presents different challenges. We mapped out which parameters determine whether it succeeds, and how to reproduce that. Others can now build on this, in developing ‘smart’ organs.”
One of the most striking results of her research is that a genetically modified organ can signal when rejection begins. The organ then releases a biomarker that can be measured with a simple blood test. This may allow rejection to be detected earlier and less invasively than with the current standard method, which requires a biopsy.
“Our ultimate goal is an organ that not only tells us when something is wrong, but can also treat itself locally. This would mean that a patient’s entire immune system would no longer need to be suppressed.” According to Irina, this is a first step towards donor organs that not only function better, but also actively contribute to the patient’s treatment.
Alongside genetic modification, Irina investigated ways to preserve donor organs for longer. By combining new cooling techniques with machine perfusion, she extended the preservation time of complex transplants, such as hands or faces, from six hours to several days. This offers important benefits. Doctors have more time to find the most suitable recipient, operations can be planned more effectively, and fewer donor organs need to be discarded. As Irina puts it: “More time means better care, not only for surgeons, but above all for patients, who can receive a donor organ that is a better match.”
Irina’s fascination with this field began during medical school. A lecture by Professor Edward Nieuwenhuis on gene therapy brought together two interests that still drive her today: “I wanted to do something with the then-new world of gene therapy and with plastic surgery. This PhD research brought those two fields together.”
During her PhD, a second ambition also grew. She sees great opportunities to bring the knowledge of plastic surgery and transplant medicine closer together. “Plastic surgeons transplant tissue every day. By combining knowledge from both fields, we can further expand the possibilities for patients.”
Although the technique is still experimental, the research is now being scaled up to larger animal models. Irina hopes that the first applications in humans will move closer within the next few years. “My ambition is for us to be able not only to preserve organs indefinitely, but also to adapt them to the needs of the patient. If we succeed, organ transplantation could eventually become as routine as a hip replacement, and in some cases, it may not be needed at all.”
In the future, the technique might also be used on a patient’s own organ. “For example, when it is already known that someone has an inherited mutation that may cause disease later in life,” says Irina. “During an operation, doctors could temporarily isolate the organ and genetically modify it. The organ could then continue to do its job in the body. This is called autotransplantation. In some cases, this could prevent the need for a donor-organ transplant.”
For Irina, this is exactly what Preserve, Edit, Transplant stands for: enabling more patients to receive a suitable transplant, with fewer complications and a better quality of life.
On 2 April, she received her PhD from Utrecht University, followed by a symposium on the same subject.
