Preserving, repairing and regenerating donor organs

Health & Technology Flagship Organ Transplantation

Only a small proportion of all donor organs meet the quality requirements for transplantation. The scarcity of organs means that 20% of patients die while they are still on a waiting list for a transplant. The Organ Transplantation Flagship Programme is focusing on reducing the shortfall. A first step is to improve the preservation of organs that are suitable for transplantation. The next goal is to upgrade unsuitable organs. This requires the use of technology, but also the meticulous balancing of ethical, economic and societal considerations.

By 2040, 25% of the Dutch population will be over 65. Older people are more often ill and they are therefore at increased risk of organ failure. This group comes on top of the younger patients who already suffer organ failure earlier in life due to illness. The result is an increase in demand for donor organs. However, that demand cannot be met. ‘The number of registered donors is rising but the number of donations that actually takes place has not changed,’ says Jan IJzermans, Professor of Transplantation Surgery at the Erasmus MC and lead of the Organ Transplantation Flagship Project. ‘Even though people are willing to donate organs, organ quality can be low because of the age, disease, obesity, smoking and alcohol consumption of potential donors.’


Only high-quality donor organs are transplanted at present. That quality depends, in part, on the time spent by the organ outside the body. A heart can sustain six hours outside the body, a good kidney as many as 24. After that, cell loss sets in. IJzermans: ‘It would be great if we could keep organs in good condition for longer. To achieve that, we have to supply an organ with oxygen and nutrients outside the body and eliminate waste products. Organ perfusion makes this possible. We want to develop a device resembling an incubator  to monitor and regulate the condition of the organ continuously using feedback mechanisms. Just like in the body itself. Our goal is to maintain the condition of organs for three to five days.’

Normal functioning

‘There are already techniques and devices for organ perfusion,’ says Paddy French, Professor at the Bioelectronics Laboratory of TU Delft and co-lead of the Flagship Project. ‘But they aren’t good enough yet. For example, we lack a broad spectrum of assessment options to determine the exact condition of an organ.’ The problem here is that those assessment options can be developed only once it is clear exactly what we need to look at. IJzermans: ‘We know a lot about organ pathology: what happens when an organ doesn’t work. We still don’t know enough about the normal, healthy functioning of organs and how to measure and improve that functioning.’

Organ on a chip

That is why TU Delft is also working on systems for the detailed study of how organs work. French: ‘We use organ on a chip models, among other things, for that work. Miniature organs are grown from stem cells on a membrane. Circulation is introduced and these organs then work like organs in the body, allowing us to follow exactly what they do. We are also working on ways to assess the quality of real organs without the need for contact. Imaging techniques, for example, to screen the organ while it is safely in the perfusion machine. That’s still unexplored territory.’

Stem cells

A step towards the next goal involves preserving organs and assessing the quality of the organs. IJzermans: ‘Our ultimate aim is to improve the condition of what we refer to as “marginal” organs to upgrade unsuitable organs. Take a donor liver with a lot of fattening due to obesity. Perfusion can eliminate that fatty tissue from the organ, making it healthier and therefore suitable for transplantation. In time, we will also be able to use stem cells to repair damage. And the possibility of growing new organs from stem cells is on the horizon.’


‘A promising avenue from a medical and technical point of view is to repair, and even grow, organs,’ says Esther de Bekker-Grob, Professor of Health Economics & Health Preferences at Erasmus University and a co-lead of the Flagship Project. ‘However, every step and technical development involves all sorts of ethical, economic and societal issues. Do we want to go down that road? What are the implications for the patient? Do we as a society think this is worth the cost? We work with ethicists, legal experts, psychologists, health economists and choice modellers. But also with patients and lobby organisations. The goal is to prolong patients’ lives and enhance their quality of life. But at what price, and which other limits apply?’

Balancing different considerations

De Bekker-Grob believes there is a basic question here: is it cost-effective? IJzermans: ‘Organ transplantation is expensive. A team is on hand 24/7 for an average of three to four donors a week. Another team is on constant standby to perform the transplant. In the future, a team may also have to be on standby for the perfusion machine. On the other hand: increasing the supply of available organs also saves money. A dialysis patient costs eighty thousand euros a year. A kidney transplant costs about the same amount the first year but much less after that: about twenty to thirty thousand euros a year.’ De Bekker-Grob: ‘As a society, we have to balance those considerations. But that shouldn’t be a financial decision alone: all kinds of additional factors need to be taken into account.’


Medical-technological innovations always involve issues like this. ‘So this convergence is a very natural alliance,’ says De Bekker-Grob. ‘Of course, the three universities already had contacts in the past. But this project has allowed us to establish strong interdisciplinary links. That is a catalyst for radically new strategies.’ IJzermans: ‘This project has a major impact in itself but there are also numerous possible spin-offs that we can start working on in the Convergence, with new funding.’ French: ‘Even at TU Delft, this project has brought me into contact with people I have never worked with before. The project has a strong presence at a lot of places in the three universities.’