One of the great achievements of modern medicine is undoubtedly organ and tissue transplantation. Not only has it saved hundreds of thousands of lives in recent decades but it has also radically transformed the everyday lives of many people, freeing them from long, invasive and exhausting treatments such as dialysis or the need to be permanently connected to an oxygen machine in cases of advanced lung disease, allowing them to regain their independence and enjoy a full and active life.

According to the World Health Organization (WHO), 172,000 transplants were performed worldwide in 2023. However, although this figure may be impressive, we are still a long way from meeting the global demand of 2 million transplants per year.

Transplantation has a long and fascinating history. The world’s first successful transplant took place in 1954 in the United States: a kidney transplant between twin brothers. Spain’s first successful transplant was in 1965 and, since then, the country has established itself as an international benchmark in this field. In 2024 alone, 6,464 transplants were carried out, made possible thanks to the generosity of 2,562 deceased donors and 404 living donors. These figures place our country at the forefront in terms of both donations and the number of transplant operations. But what challenges do we still have to address to continue advancing, both nationally and globally? How can we broaden access to transplantation and meet the needs of all patients?

From a medical point of view, one of the greatest challenges continues to be preventing the recipient’s immune system from rejecting the organ. And in addition to this problem is an equally critical barrier: the shortage of organs. In 2023, more than 100,000 people in Europe were on a waiting list for a transplant but fewer than half managed to get one. This situation could worsen in the next few years due to an ageing population and an increase in chronic non-communicable diseases, many of which eventually require a transplant. This is the case, for example, of chronic kidney disease (for which a kidney transplant is a treatment option) which, according to estimates, could become the fifth leading cause of death worldwide by 2040.

In the face of such challenges, science is advancing on many different fronts. From the development of more effective immunosuppressive therapies with fewer adverse effects to research into xenotransplantation (using organs from genetically modified animals) and bioartificial organs manufactured in the lab.  Work is even being carried out to improve logistics and increase organ availability by optimising the entire donation and transplantation process.

On 8 May, the CaixaResearch Debate explored all these challenges and opportunities, as well as the latest advances being made in the field of transplants, with four leading researchers: 

• Beatriz Domínguez-Gil González is the Director General of Spain’s National Transplant Organisation (ONT), an agency under the Ministry of Health that coordinates and organises the donation and transplantation of organs, tissues and cells.
• Oriol Bestard Matamoros is Head of the Nephrology and Renal Transplant department at Vall d’Hebron University Hospital (HUVH), leader of the Nephrology and Renal Transplant research group at Vall d’Hebron Research Institute (VHIR) and Associate Professor of Medicine at the Autonomous University of Barcelona.
• Xabier Aranguren López is Principal Investigator of the In vivo Organ Generation by Stem Cells group at the Centre for Applied Medical Research (CIMA), University of Navarra. Among other things, he is studying the generation of human organs in pigs using genetic techniques.
• Concepción Gómez Gavara is a Surgeon in the Hepatobiliary Pancreatic and Transplant Surgery department at Vall d’Hebron University Hospital (HUVH) and a Researcher at the Vall d’Hebron Research Institute (VHIR). She’s also involved in the Livercolor project, which uses artificial intelligence to improve the selection of transplantable livers.

The discussion was moderated by Núria Jar, a Journalist specialising in science, health and international news.

Below are the main conclusions reached during the CaixaResearch Debate. Why not join us and find out more?

 

 

The donation and transplantation system in Spain

 

Why is the so-called Spanish model of organ donation and transplantation successful?

“We’re a very supportive country, a society that’s willing to help, but that alone isn’t enough to make us leaders in organ donation. One of the keys to success is the National Health System, which is public and universal. We should also mention the organisational factor, our donation and transplantation system, which enables a person who’s willing to donate after their death to become a real donor” – Beatriz Domínguez-Gil González

“Few of the people who die can become donors. In order to become a donor after death, you have to have died under extremely specific conditions, in the intensive care unit, usually connected to mechanical ventilation and with no medical contraindications for donation. Only 1-2% of people who die in hospital do so under such circumstances” – Beatriz Domínguez-Gil González

“Our system is designed to systematically identify those people who die under these unique circumstances, approaching the bereaved family in a very professional way and ensuring the different phases of the donation process are carried out as flawlessly as possible. Our approach hinges on the transplant coordinator in the hospitals and the coordination, at a supra-hospital level, carried out by the National Transplant Organisation and the Coordinating Bodies at a regional level. It’s an organisational model that enables the solidarity of citizens to be transformed into the reality of donation and transplantation” – Beatriz Domínguez-Gil González

 

From how young and up to what age can organs be donated?

“In principle, there’s no age limit for donating as each donor’s characteristics are assessed on an individual basis. It’s true that, as people age, there are age-related changes in their organs so that, when you get older, it becomes increasingly difficult to be a heart or pancreas donor, for example. Even so, transplant teams have learned to successfully transplant highly complex organs from very old people” – Beatriz Domínguez-Gil González

“There are very few absolute contraindications to organ donation. That only happens in cases of donors with metastatic tumours, extraordinarily aggressive tumours or certain infections” – Beatriz Domínguez-Gil González

 

Who has priority in receiving an organ?

“There’s a huge disproportion between the patients who need a transplant and the organs available, which is why all transplant systems have organ allocation systems that take the medical factors into account and guarantee fair access” – Beatriz Domínguez-Gil González

“Spain has a mixed model of organ allocation: national and also regional/local. On the one hand, at a national level organs are allocated for patients in a critical situation, with a very high risk of death within a short period of time. As soon as a compatible donor appears, that organ goes to that patient. Priority is also given to patients who are difficult to transplant, patients who tend to reject most of the organs available. As soon as we find a suitable donor for that recipient, they’re given priority over all the others. Finally, at a national level, priority is also given to children because they’re very difficult to transplant, and to patients who need combined transplants” – Beatriz Domínguez-Gil González

“After these prioritised patients, organs are allocated regionally and locally with the aim of reducing ischaemia times [the period during which the supply of blood, oxygen and nutrients to an organ or tissue is interrupted] as well as organ transport costs. This regional and local allocation also follows clinical criteria, i.e. priority is given to the patient who’s in the most precarious situation and at the greatest risk of death” – Beatriz Domínguez-Gil González

 

 

The medical challenges of donation

 

What’s the problem in selecting organs that are truly optimal for transplantation?

“An organ is usually assessed by means of its morphological characteristics. For instance, we know that livers that accumulate more fat tend to be more yellow and have more rounded edges, and we also know that livers with more than 30% fat accumulation can fail. The objective way to assess this is through a liver biopsy, i.e. taking a small sample of the liver and analysing it under the microscope” – Concepción Gómez Gavara

“However, very often this procedure isn’t available; we need to work fast and against the clock. In such cases, the organs are assessed based on the opinion of the person (the surgeon) evaluating the liver, which can sometimes lead us to discard organs that could be valid for donation. That’s why, since 2018, we’ve been developing the Livercolor project that aims to train an artificial intelligence (AI) algorithm which, based on an image, can give us an objective answer about a liver in a matter of seconds to assess whether it’s suitable for transplantation” – Concepción Gómez Gavara

“Thanks to the support of “la Caixa” Foundation’s CaixaImpulse Innovation programme, this project is now a reality. We’ve created an app to take photos of cases at the hospitals collaborating with us. The results obtained are much more accurate than the standard evaluation method. Even so, the final decision will always be made by the professional; in other words, these AI tools are used as a support” – Concepción Gómez Gavara

 

Could this AI method be used for other organs apart from the liver?

“We need to train the algorithm with a lot of data to ensure its results are extremely accurate. We believe that, by the end of 2026, we’ll have 1,000 cases, which will probably be enough to begin using it clinically. We started with the liver but we’ve also started to develop it for kidneys. It’s a question of training algorithms to analyse macroscopic images, so in principle it can be extended to any organ” – Concepción Gómez Gavara

 

What strategies are followed to prevent rejection of the transplanted organ?

“Today we’re able to differentiate quite precisely those patients who are susceptible to developing rejection because they have a pre-existing condition that can cause rejection, and we’re able to generate a precise immune response so that rejection doesn’t occur. However, we find it relatively hard to identify another large group of patients who don’t have any prior conditions that may indicate rejection” – Oriol Bestard Matamoros

“One of the major lines of research in transplantation worldwide seeks to improve the identification of each patient’s immunological risk in order to design treatments that suppress the immune system’s response to the organ. They’re studying everything, from the genetic differences between donor and recipient to the activation of lymphocytes, which are the cells that can cause rejection. There’s a whole line of very active research but we still haven’t been able to incorporate it into clinical practice” – Oriol Bestard Matamoros

 

What are the risks involved in immunosuppressive medication?

“Today, the vast majority of patients receive exactly the same amount of immunosuppression treatment. We need to learn to identify those who could live with just one low-dose drug and those who need different combinations of drugs. The treatment is the same for everyone and transplant specialists have to deal with any complications that arise. For example, the rejection rate in a first-time transplant patient is around 5-6% but the immunosuppression treatment they receive produces other side effects for the metabolism or cardiovascular system that also have to be managed” – Oriol Bestard Matamoros

 

What solutions are you working on in this respect?

“We’re looking for a family of drugs or a molecule that acts directly on the immune system and avoids side effects. This may have to come at the cost of some changes to the paradigm doctors work with and we may have to accept a slightly higher rate of controlled rejections. Our project, which is supported by “la Caixa” Foundation’s CaixaImpulse Innovation call, takes advantage of molecular biology and technological developments at the protein level to create a complex molecule that inhibits the immune system in a specific way. Our aim is to slow down the activation of T lymphocytes whilst, at the same time, allowing the regulatory cells to continue their activity. In other words, we take care of the patient’s protective response whilst controlling the immune response that leads to rejection” – Oriol Bestard Matamoros

 

 

The challenge of organ shortage

 

The WHO states that two million transplants are needed to meet global demand but we’re far from achieving those figures. What solutions are being investigated?

“There are three major strategies. The first is xenotransplantation, the transplantation of organs from animals to humans. This mainly involves the transplantation of pig organs that have been genetically modified to avoid rejection in humans. The second is 3D-printed organoids, a technology that involves using different types of cells, 3D printers and biomaterials to create three-dimensional structures that resemble organs. At present it’s still only possible to produce very small organs but the idea, in the future, is to be able to produce organs that are the right size and can be used for transplantation. And the third strategy is the direct generation of human organs inside animals, using stem cells” – Xabier Aranguren López

 

How does the direct generation of human organs inside animals work?

“The aim of our line of research, supported by “la Caixa” Foundation’s CaixaResearch Research call, is to gdiffconcepenerate human organs inside animals using a technique called blastocyst complementation. This consists of genetically modifying the embryos of a host animal (in our case a pig) so they can’t develop the organ we’re interested in. At a very early stage in the embryo’s development, human stem cells are microinjected into it. From then on, the animal begins to develop but, since it can’t form the organ on its own, this is generated by the human cells. In this way, we could generate human organs inside animals that could be used for transplantation” – Xabier Aranguren López

“It’s a highly complex technology and there are still lots of hurdles to overcome. One of the big limitations is that human cells have a very low capacity for integration within animal embryos. Once we’ve resolved this, we can start talking about generating human organs in animals such as pigs. It’s difficult to estimate timescales but a lot of progress has been made in recent years and it could be that, within the next 5 to 10 years, we’ll start generating human organs in animals” – Xabier Aranguren López

 

 

The challenges of the future

 

What needs to be done to further improve the work being carried out in relation to donation and transplantation?

“In terms of healthcare practice, the human challenge is becoming increasingly important. Transplants have grown exponentially but the teams are almost the same as they were 10 years ago. Moreover, there’s the considerable challenge of generational change. Transplantation has gone from being, clinically, a very attractive activity for healthcare professionals to becoming such a normal therapy that it seems to have lost its professional appeal” – Beatriz Domínguez-Gil González

“From the point of view of research, there are several challenges. One is the change in donor profile, as Spain has a very long life expectancy and mortality in young people from preventable causes is low. Consequently, the majority of donors are older and we have to ensure their organs function properly in the recipients. Another challenge is to improve so-called asystole donation. In other words, preserving and validating organs donated by people dying from circulatory death, organs that have suffered from a lack of blood flow and oxygen” – Beatriz Domínguez-Gil González

“Another improvement would be to encourage living donors. We have a large and growing number of donors but people aren’t aware of the importance of living donations, for instance of a kidney, and these have the best survival rate. It would also be important to improve the lifespan of the organs transplanted so that patients don’t need another one at a later date. To do this, as we’ve already discussed, we need to understand better how immunosuppression works and why some patients seem to require much less treatment than others” – Oriol Bestard Matamoros

“The inclusion of new technologies can help us make transplantation professionally attractive again. Projects like Livercolor show the way forward. Doctors want to use new technologies to make safer and more accurate decisions. I believe this will be key to ensuring young professionals join the field” – Concepción Gómez Gavara

“In addition to increasing the number of donations from living people, it’s also important to improve organ preservation to help shorten the waiting lists” – Xabier Aranguren López

 

How has asystole donation improved?

“The first transplants from deceased donors, in the 1960s, were carried out with organs from people who’d died from circulatory death. The results were disastrous and asystole donation became a thing of the past. It was then that brain death donation (a condition that enables organ function to be artificially maintained after the patient has become neurologically dead) established itself as the main route for organ procurement. However, from the 1990s onwards there was a renewed interest in asystole donation, as this was believed to have great potential in terms of increasing organ availability and cutting waiting lists. Today, only 26 countries in the world have asystole donation programmes. Spain is the country with the highest rate of this type of donor in the world and the only one that has managed to transplant all types of organs from such donors. Last year, in fact, for the very first time, there were more asystole donors than brain death donors” – Beatriz Domínguez-Gil González

“Spain has managed to transplant all types of organs from these donors thanks to very specific preservation strategies, particularly one called normothermic regional perfusion, which was discovered here in the 1990s. That’s why it’s important to talk about this type of donation and all the research potential it has in the field of organ preservation and validation” – Beatriz Domínguez-Gil González

 

 

The great debates surrounding transplantation

 

In recent years we’ve seen, for example, the birth of the first baby from a transplanted womb. What are the dilemmas posed by such developments?

“We’re used to thinking of transplantation as something valid for organs that are vital for survival. These other types of transplants raise economic dilemmas, regarding whether or not the public system should pay for them, and ethical dilemmas such as whether someone really needs to have a child. All have pros and cons. Even so, I don’t think it’s fair to compare one type of transplant with another; it’s not fair to weigh them on the same scale” – Oriol Bestard Matamoros

“When very disruptive innovations appear, there’s always a period of rejection. When Cristiaan Barnard carried out the first heart transplant and patients died within days, the ethics of what he was doing were questioned. Today we’re cautious about uterine transplantation but maybe, in ten years’ time, it will have become normal. Even so, we should remember that sterility is recognised as a disease, so what needs to be discussed is the proportionality of the measures that need to be adopted to treat that disease” – Beatriz Domínguez-Gil González

“Another issue is what uterine transplantation involves nowadays. It’s performed with a living donor who has to undergo a very aggressive hysterectomy. What’s more, the recipient undergoes immunosuppressive therapy which means that, if pregnancy finally occurs, the foetus will develop within a context of immunosuppression. Finally, the recipient has to have the uterus removed again once the function has been fulfilled. So the question, I think, must be whether this is proportionate to what we’re trying to resolve. I believe that, over time, many of these issues will gradually be understood and today it’s not easy to take a stance that’s entirely for or against” – Beatriz Domínguez-Gil González

 

What are the dilemmas of growing human organs inside other animals?

“All new things that appear in medicine are rejected to some extent at first. In the case of generating human organs in pigs via stem cells, we’re talking about producing organisms that are pigs but also partially human. Moreover, human stem cells can always go to other regions we’re not interested in, such as the brain, and having a pig with a part of the human brain would be highly controversial ethically. What we have to do is to explain very well what we’re doing and how we’re doing it. I think that, once the first clinical trials are carried out, if these organs work and manage to save lives then, little by little, they’ll be seen as something more normal” – Xabier Aranguren López

 

And does the use of AI in medicine raise any concerns?

“Those who accept AI best are the patients, who are always much more open than professionals when it comes to considering new technologies. It’s true that, for highly experienced professionals, a tool that tells them something different to what they consider to be right can create conflict but, in fact, algorithms are going to be trained with so much data that it’s impossible to claim that, in our professional lives, we could manage to assess so many cases” – Concepción Gómez Gavara