Liver diseases have a significant impact on a patient's life. Treatments don't always succeed, and sometimes organ transplantation is the only way out. Prof. Dr. Luc van der Laan researches the most suitable treatment using organoids and seeks to better understand liver diseases. "A lot of trial and error is required, but ultimately, you make progress. It's a matter of persistence."
Luc van der Laan is a professor of regenerative medicine and head of the Laboratory of Experimental Transplantation and Intestinal Surgery (LETIS) at Erasmus MC. He was recently appointed as a Medical Delta professor with an affiliation at TU Delft. Van der Laan is one of the Scientific Leaders of the scientific program Medical Delta Regenerative Medicine 4D: Generating complex tissues with stem cells and printing technology.
"For me, this appointment is a recognition of my work and expertise and a confirmation of collaboration with my partners at TU Delft. With this appointment, our collaboration will hopefully become more visible, leading to new opportunities to expand on our ambitions. This could include joint grant applications, scaling up projects, or exploring new applications.
Besides my role as a researcher, I am also active in education. I want to leverage the visibility this appointment brings to encourage medical students to take more interest in medical technology."
"I am a professor of regenerative medicine, focusing on the liver. In regenerative medicine, we aim to use stem cells to treat diseases and study disease processes outside the body. We apply this, for instance, in liver cancer. The effectiveness of treatments varies from person to person. By growing small tumor fragments, known as tumor organoids, from cancer stem cells, we can investigate which treatment works for a specific patient. In the future, this approach could help find the best treatment for each patient. This concept can also be applied to other diseases, such as fatty liver disease, a consequence of obesity and an unhealthy lifestyle, leading to liver inflammation and failure. Currently, there is no effective treatment, and we need to better understand this disease."
"To test a wide range of medications simultaneously with organoids, you need organ-on-a-chip technology. TU Delft plays a significant role in advancing this technology. Additionally, we aim not only to create organoids from a single organ but also to merge multiple organs. Collaborating with a PhD student from TU Delft, we are studying the interaction between the kidney and liver in a multi-organ-on-a-chip setting. For example, if there is liver damage due to medications, it may also cause damage to the kidney. The mechanism behind this is not entirely known, and we want to study it with this setup.
This is also useful for research on organ transplantation. Erasmus MC is the largest transplantation center in the Netherlands. Both the kidney and the liver play a significant role in the medication used during transplantation.
With bioprinting, we can scale up and create more complex tissues in the culture dish. This enables us to examine the interaction between different cells and an organ.Another technique led by Delft is 3D and 4D bioprinting. With printing devices, we can print cells in a specific structure, allowing us to study various physiological aspects. We start on a small scale, but with bioprinting, we can scale up and create more complex tissues in the culture dish. This enables us to examine the interaction between different cells and an organ."
"We have successfully conducted research with organoids in the laboratory, but there are still significant challenges. We cannot yet grow organoids from every patient, and translating what we measure on the chip to the patient needs further investigation. We have succeeded in performing measurements. We tested 130 different drugs on cancer organoids, and it became clear that certain drugs worked much better than others for this individual's organoids. Whether this insight is beneficial for the patient is something we still need to explore. We will be working on this for the next five to ten years, not only in collaboration with Delft but also internationally.
We also use organoid technology in organ transplantation. It offers opportunities to repair donor organs before transplantation. Although this is still in the future, we hope to make progress in this area. To keep organs outside the body viable, we use an organ perfusion system. Organs are kept alive in it for a few days, providing an opportunity to repair the organ. Or, in the future, to better tailor the organ to the recipient. Organ rejection is a significant challenge, and many medications are currently required. Gen-editing might be possible in the distant future, but that's at least 5 to 10 years away. In the short term, regenerating an organ outside the body is relevant for liver transplantation. This involves taking a small healthy piece of the organ, allowing it to grow, and then placing it back, for example, in liver cancer."
"For many projects related to liver diseases, we try to establish connections with patients. We have good contact with the Dutch Liver Patients Association. We keep them informed about new developments and try to generate enthusiasm for ongoing research. Patients are the best advocates for new developments. If you have a disease, you want to get better as soon as possible and find it essential that research is conducted. Patients can also pose very interesting or surprising questions that make you think. This is enjoyable and can be very valuable.
Patients are the best advocates for new developmentsIt's also important for us to involve physicians. They provide research materials and must ultimately apply innovations. For example, we have discussed the use of organoids with surgeons and oncologists to find better treatments for liver cancer. The current challenge is that we cannot grow organoids from all patients. They see this as a significant limitation. When doctors apply this technique, they want to offer it to all patients. In the dialogue, you learn what they consider important and where we still need to work."
"I find collaborating with scientists from outside my field very stimulating. Game-changers indeed arise at the intersection of different fields. Engineers develop methods, and medical professionals can apply them.
Sometimes you encounter challenges. We are working on 'Regenerative Medicine 4D' within Medical Delta, where the fourth dimension stands for time. Three-dimensional shapes can change over time. However, for these changes to occur, organoids must remain alive. There are still challenges in this area, requiring a combination of technical and biological knowledge. A lot of trial and error is needed, but ultimately, you make progress. It's a matter of persistence."
"I find the new direction of Medical Delta, with more focus on societal application, very positive. As a scientist, you always must ask yourself about the societal value of your work. For very fundamental research, this might be less evident. I see myself as a translational researcher, evaluating how fundamental research can be applied to patients. The new direction aligns well with that.
The new direction has also given me new ideas. For a few years now, I have been interested in microplastics, small plastic particles, and how they affect human health. This interest stems from my focus on liver diseases, as the liver is crucial for processing nutrients. Everything you ingest through your diet passes through the liver, including toxins and contaminants like microplastics.
How the liver deals with microplastics is still largely unknown. The body cannot break down plastic. While particles may become smaller over time, the body cannot digest them. This is a new and underexplored aspect. We are increasingly exposed to microplastics, but we don't know their effects. Does this lead to accumulation in tissues? Or does the liver play a role in excreting them? This is an interesting new field for Medical Delta, and I would like to play a role in it."
The health problems for the coming decades require a genuinely new approach
"Medical students are very focused on the medical aspect and try to gain control over it. Engineers are looking for a solution. A doctor must make a diagnosis, make choices, and communicate with the patient. Technical students are more concerned with how they can address problems from their field, initially with less connection to the patient. But engineers are essential for the future of medicine. You need both, the observers, and the doers. The health problems for the coming decades require a genuinely new approach. Therefore, it's good that medical students are increasingly exposed to technology. Clinical technologists play a crucial role as a bridge between the fields of medicine and engineering."
"I live in Delft and read the newspaper 'Delft op Zondag.' There was an article about the work of Marie-Eve Aubin-Tam from the Faculty of Applied Sciences at TU Delft. She uses bioprinting to print algae, which can generate photosynthesis and oxygen synthesis. I found that to be an interesting development. I talked to her to see if we could also do something with photosynthesis in the constructs we are developing for organoids. Currently, nothing has come out of it, but these kinds of introductions can lead to unexpected eye-openers."