Prof. Dr. Luc van der Laan: "When you can make organs, you have a good alternative for transplantation"

Prof. Dr. Luc van der Laan is professor of Liver Regenerative Medicine at Erasmus MC and works as a Scientific Leader within the Medical Delta program Regenerative Medicine 4D. His inaugural lecture "Heal the whole Liver" will take place on November 29. That title contains both sides of his research: the cure of liver diseases and the generation of a complete organ.

Making a complete organ: is that possible?

Yes, but we are talking about the long term. Our research focuses on two areas. The first is reconstruction, which involves tissue engineering - constructing a functioning piece of tissue from different building blocks. Think of it as a kind of bio-Lego: we turn stem cells into scaffolding and fill it up, into a piece of liver. Eventually you should be able to make a complete liver with that technique.

The second area is about disease modelling. We use this to look at disease models on a micro scale. We do this by making a mini-organ from stem cells, or a part of it with only the functional properties. We can study the course of the disease and, for example, test medication. This way you can see how a disease develops, how you can control it and possibly cure it.

What will it mean if it is indeed possible to make an entire liver in the future??

I am a biologist and I am employed in surgery. The doctors I work with are engaged in organ transplants, mainly from livers and kidneys. For kidney malfunctions there is an alternative in kidney dialysis, but there is nothing for the liver. If a liver does not function properly, it leads to death. We are faced with a huge donor deficit and, moreover, a shortage of good quality donors. There is also the risk of rejecting a donor organ. If you can make organs, you have a very good alternative.

Because it is not yet possible to make an entire organ, we are now focusing on parts of it. For example, the bile duct is very important for the functioning of the liver. The structure is less complex and you need fewer cells to make a functioning piece of bile duct. Within a few years it will be possible to replace part of the bile duct.

What is Medical Delta's role in this research?

For my research it is very important that regenerative medicine has become a Medical Delta program. For example, I can now do research into hepatic steatosis (fatty liver) as the cause of a number of liver diseases. Colleagues in Leiden are engaged in regenerative medicine in the field of bone and cartilage. That is a lot different, but in the end we all work with complex tissues in a culture container and we can learn a lot from each other.

I am very happy with this kind of reinforcement of research teams. The infrastructure of Medical Delta also helps us, especially in the technical area. Once you make tissue that is somewhat larger, you must create a heart / lung system. A lot of technology is involved. This is possible within the Medical Delta collaboration. That is a hit: in the meantime, the Maag Lever Darm Stichting (Foundation for Stomach, Liver and Bowel) has indicated that it wants to participate.

Don't people think it is very creepy, an organ from a laboratory?

These types of themes have a certain "yuk factor". But ethical considerations are fairly theoretical. As soon as people become patients themselves, it becomes completely different. Then you are happy with the possibilities. What makes a difference is that in this case we limit ourselves to human cells and even to the cells of the patient in question. By building an organ from these cells for the patient, you bypass rejection symptoms and medication against rejection, medication that also has many side effects. With cells from your own body you can test on a micro scale how a disease will respond to a certain treatment before you try it on the patient.

How far are the developments now?

Many people are very optimistic, but you also have to be realistic. Because except with stem cells, of which still holds some secrets, you have to deal with the environment of those stem cells. That ultimately determines what the stem cell will or cannot do. That is the challenge in the coming years. A breakthrough in that research will ensure that we speed up.

In practice, the first results with disease modelling are already a reality. It is still in the experimental phase. Creating an organ will take longer. Of course I hope to experience it, although I expect it to become reality after my retirement, rather than before. It would make organ transplantation redundent, but even after the first patients get a cultured organ, you have to wait at least five to ten years to see if it really works well.

It would be great to be able to experience it

Sure. Everyone who works in biomedical science is motivated in one way or another to have an impact. Everyone has friends, acquaintances or family members who are sick. I myself have lost a brother to colon cancer and therefore know how vulnerable people are. You should not have the illusion that you are going to make those people better, but you can make a contribution in the longer term. With small steps, your research can indeed have an impact on society and ultimately on individual patients. That motivates enormously.