Prof. Ingrid Meulenbelt

Prof. Yolande F.M. Ramos

Danielle Nicholson, Pintail Limited spoke with Leiden University Medical Center Profs. Ingrid Meulenbelt and Yolande F. M. Ramos via Zoom to kick off our series of interviews with women researchers in AutoCRAT.

Danielle: Ingrid, Yolande, thank you for agreeing to speak with me about your work and congratulations on the publication of your recent paper. That’s really exciting news and very important for AutoCRAT.

Danielle: What is your assessment of the current state of osteoarthritis (OA) treatment and care?

Ingrid: It’s quite poor. There’s not much out there for people with OA. They are suffering from pain and problems in mobility already at 55 years of age and onwards. There is nothing for them yet so they are being almost patronized by the offer of physiotherapy and then painkillers. They are kept in a patched-up state until they are eligible for joint replacement surgery from about 70 years of age. This is currently the only disease-modifying treatment that we have right now. I think particularly the people with OA between 55 to 70-years of age who are still part of the workforce do not have any real options. In that respect, care is minimal. We know this from our patient and public participation arthritis group (PPA-Leiden). These people are searching the web for any treatment out there, something that they can do themselves. There is a lot of false hope.

Danielle: Why did you establish the PPA group?

Ingrid: Initially, it was the funding agencies in the Netherlands who believed that it was important to involve patients in research project design. But once we started the PPA group, we realized it was a highly valuable exercise for us and for the PhD students to engage with the patients because we are not medical doctors. The group provides an additional dimension to the work we are doing. This is an enrichment forwards and back. The group helps us to communicate our fundamental research, especially our abstract -omics work, in an understandable way.

Danielle: With regards to your recent publication, “Cartilage from human‑induced pluripotent stem cells: comparison with neo‑cartilage from chondrocytes and bone marrow mesenchymal stromal cells” Cell and Tissue Research, July 9th, 2021 its graphic (below) gives a helpful snapshot of the study design. It is a great tool to communicate the results to non-specialists.

Ingrid: It also helps us make the protocol for the medical ethical committee which inputs into the patient information leaflet.

Danielle: Can you please talk a bit about your research group and your roles within it? Where are you situated?

Ingrid: I’m the Head of the OA Research Group at the LUMC. Yolande is the most senior researcher in my lab and in that respect, she is also partly in charge of the staffing and guides the PhD students. She also does research in the lab. She is my right hand in that respect.

We are situated in the Research Tower next to the LUMC. In the OA Group, apart from Yolande, there are 3 more senior researchers, and we have 7 PhD students and a technician. We are situated within the Biomedical Data Science Department, a result of my background in genetic epidemiology. I started off trying to determine the genes that are causing OA. We gained an in-depth understanding of this in part due to the benefit of the data science people around us. When we identified a couple of the genes that we thought were interesting and could be involved in the underlying pathophysiology of OA we shifted focus to try to determine the function of these genes. What were these genes doing in the cartilage tissue? This work made us realise if you want to do functional work you need tissues to work with. This was why we started the Research in Articular Artrose Kraakbeen RAAK study, for OA articular cartilage research: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0103056). Because we are near the hospital, we can obtain materials from people that undergo joint replacement surgery as a result of OA. If a patient is undergoing joint replacement surgery in the morning, we get a call when the surgery is finished. From the surgical waste material, we can obtain cartilage and bone, but also cells. We create molecular profiles from the cartilage and bone, as in AutoCRAT, and with the cells, we generate disease models. We tried to regenerate cartilage and bone from the cells that we took from the patients. Because we wanted a more sustainable source of cells, we started with stem cell research, employing Yolande’s cell biology expertise. We evolved from a molecular, cellular, and genetic epidemiological group to a much more fundamental biological group. This combination of molecular epidemiology, -omics and cell biology has made our OA group stronger in research proposals. In AutoCRAT, we use our cell biology expertise with stem cells and combine this with -omics data to determine the mechanisms of action of the cells involved.

Danielle: What is your favourite aspect of your work?

Yolande: My work is very diverse: there is never a dull moment. No two days are ever the same. One day, I could take part in an interview, another I am talking to patients. Then, I am going to the lab to check my cells. I never have the same day twice. Science fascinates me, and as a result, the work is fulfilling.

Ingrid: Our work is dynamic and you are at the forefront of what is known, but the pitfall of what we do is that the work is never finished!

Danielle: The LUMC are ahead of the cellular therapeutics curve in many ways. What are some practical hurdles that must be overcome to make cell therapies widely available?

Ingrid: I try not to think too much about it yet. If you are realistic, and you speak with other people then we have a long way to go. Our OA group are still working quite fundamentally in that sense. As soon as we think about cell therapies with iPSCs, we need to have GMP facilities, GMP cells, cleanrooms and the regulatory rules! It is unbelievable what we must do. This is not something we can do as a small group.

As for the new centre, ​​NECSTGEN (Netherlands Centre for the Clinical Advancement of Stem Cell and Gene Therapies), it is being built. It is a large institute. The idea is beautiful- a forward-planning institute, nearby, linked to LUMC and that could take care of the facilities and legislation that we would need for human studies and therapies.

Yolande: In research such as in AutoCRAT, one uses a lot of animal-derived reagents. When you shift to developing a therapy for humans, as part of the GMP and because we are accustomed to the animal-derived reagents, the alternative reagents could make the experiments and therapies much more expensive. This is another hurdle.

Danielle: In your opinion what is the most exciting aspect of AutoCRAT?

Yolande: For me, it is really exciting that so many partners within Europe aim at one same research goal. Together, we combine knowledge capacity and practical expertise to arrive at one outcome- for the patient. There is a really good synergy among the partners, and this helps to advance toward this aim together!

Ingrid: I agree, and indeed, the project has a very open atmosphere without any competition, we are pushing forward and aiming for that one goal! There is always competition going on in the field, at various levels. Mary is doing a good job to connect us and make sure we are collaborating without being protective of the work we are doing.

Danielle: What do you like to do in your free time in and around Leiden?

Ingrid: Well, I do not live in Leiden but close by, near the sea. I really enjoy being by the shore, running near the dunes and enjoying these things with everyone I love.

Yolande: I live in Amsterdam. I just love the cultural environment there. I love visiting museums on the weekends, walking around Amsterdam, enjoying the architecture and the parks.

Danielle: Do you have any advice for Early Stage Researchers looking to get into cell therapy research?

Ingrid: Don’t let others get you down. Don’t let yourself get too distracted by the grant-writing and all of the other things you will need at the end. Enjoy the dynamics of the field.

Danielle: Thank you both for meeting with me and sharing your thoughts. This is the next best thing to a face-to-face meeting which I hope will happen before too long passes!