An important research project you're currently working on is about the early detection of osteoarthritis. You recently received a significant NWO-ReumaNederland Grant for this research.

Why is this important?

Cillero Pastor: “With the KIC NWO-ReumaNederland Grant for our project CircBioCare we’ll study people at risk of developing osteoarthritis. We aim to develop advanced methods to detect blood proteins and genetic material (biomarkers) associated with the onset of osteoarthritis enabling diagnosis in primary care. By detecting signs early, even before physical symptoms appear, we can intervene much sooner, and that's where research at the molecular level comes in. 

Osteoarthritis affects hundreds of millions of people, and its incidence is expected to rise due to our aging population. The need for early diagnosis has never been so important. Naturally, for the patient, because we want to avoid as much as possible invasive treatments for them. But it's also important due to the high costs of such treatments, especially when it comes to joint replacements. These costs have a major impact on the healthcare system and ultimately on society. If we can intervene earlier, we hope to perform surgeries less frequently in the future. While doing research, the clinical translation is always on my mind. Ultimately, everything for me revolves around being able to help patients. But we still have a long way to go."

Can you provide further details on this research?

Cillero Pastor: “For an increasing number of diseases, we can offer patients a personalized therapy, but not yet for all. Osteoarthritis is one of them. In close collaboration with the orthopedics lab and the hospital, we collect biopsies⁴ from the operating theatre from patients undergoing knee surgery. Additionally, we also collect material from younger individuals who engage in rigorous sports and local damage. More specifically, we collect and investigate the role of fat tissue in the joint microenvironment. With this precious material we can create in vitro models⁵. Utilizing tiny pieces of these biopsies, we aim to identify distinct fingerprints that tell us the differences between patients. With this insight, we envision developing more personalized therapies over time. These therapies could involve designing specific drugs tailored to individual needs or implementing treatments that, through the stimulation of appropriate host cells, promote tissue regeneration or enhance the regenerative capacity of cells to address local damage. Additionally, from this patients’ waste material, we hope to discover new biomarkers. Combined with our understanding of which groups of people are more susceptible to osteoarthritis, this information may enable us to predict the likelihood of an individual developing osteoarthritis.

What's fascinating is that through single-cell research, we're discovering that it's not just about individual cells or tissues; all our organs are connected. I believe that all tissues talk to each other and send signals throughout the body. This is why I'm intrigued by the concept of using blood as a biomarker. While we currently lack an advanced system that mimics the entire joint, like an organ-on-a-chip, we can study isolated tissues in the lab. Our in vitro models show us that when we stimulate certain cells with material from fat cells, they respond, and vice versa. They show early signs of osteoarthritis. This tells us that the issue isn't just about cartilage; it's about the complexity of the joint as a whole. Our goal is to understand this complexity—from the level of single cells to the entire human body. It's incredibly complex, but also incredibly exciting."

You mentioned cell stimulation as a form of treatment. Which specific types of cells could be utilized in this therapy?

Cillero Pastor: “We utilize cells that play pivotal roles in communication and tissue restoration, as well as cells that can enhance the function of other cells. Currently, we are investigating adipose tissue located in the joint. This tissue contains fat, but also hosts other cells. Among these, one of the most crucial cell types is known as 'stem cells'. Stem cells possess the ability to differentiate into various cell types. By stimulating this cell population and promoting their differentiation into cartilage cells, we can facilitate the healing of joint damage using the patient's own cells – essentially boosting the patient's natural cell system. However, the efficacy of this therapy also depends on the patient's profile. Not all patients possess the necessary cells to transform into cartilage cells. It's understood that as individuals age, the capacity of their stem cells diminishes, whereas the stem cells of younger individuals are robust both in capacity and quantity."

Have you already discovered things that can be taken into the clinic?

Cillero Pastor: "Yes, we're working on an exciting project where we've identified specific protein markers in patients who've had surgery. What's fascinating is that we've noticed some patients respond well to surgery while others don't. By studying their protein profiles, sort of like a molecular fingerprint, we hope to predict whether surgery will be beneficial for a patient. Imagine giving surgeons a toolkit based on these markers, so they can decide if surgery is the right option for each person. Right now, it's still fundamental research, mostly done in the lab. Our goal is to find various markers not just in the joint, but also in the blood. Eventually, we hope to develop a simple blood test that can give us these insights without needing to do anything invasive to the patient. That's when it'll be ready for real-world use, but it might take another 5-10 years to get there."

What did you want to become when you were young?

Cillero Pastor: “Oh, actually I never thought of being a scientist. I wanted to be a writer. And I do that of course, I’m writing papers and grant proposals (laughing). When I, back in Spain, had to make the choice to go more into alfa or beta I thought ‘writing is quite natural to me, let’s now do the biomedical part. It’s easier to do that path and combine it later’. But then I became so deeply immersed in it, I was so excited by all the biomedical topics, that I decided to stick with biochemistry. It is fascinating that the things you are looking at are things that you actually can’t see."

Text: Eline Dekker
Photo: Joey Roberts

^{1 - An advanced analytical technique employed for molecular characterization of cells and tissues in biomedical research.}

^{2 - Such as the presence, structure, composition, behavior, and interactions of molecules.}

^{3 - Osteoarthritis is a degenerative joint disease characterized by the gradual breakdown of cartilage in the joints. It can affect various joints, including the knees and hips.}

^{4 - A biopsy is a small sample of tissue or cells that is removed from the body for examination, for instance under a microscope.}

^{5 - In an in vitro model, experiments can be performed with cells, tissues, organs or microorganisms grown in controlled environments outside the organism.}