Inside a lab at the O2 building is a sight as odd as it is intriguing: a light pink, bubble gum-like substance that rhythmically contracts and relaxes. The substance is a strip of cardiac cells; a simplified, miniature, ‘beating’ heart. This biomedical feat is the work of Jolanda van der Velden and her team, who want to use it for the development of treatments for genetic heart diseases.
‘The heart is really the most beautiful organ’
Difficult to duplicate
“The heart is really the most beautiful organ. It’s associated with emotion and it’s the engine of the body”, says Van der Velden, who is a professor at Amsterdam UMC. She has been studying mutations in sarcomeres – the basic building blocks of heart muscle cells – since 1994. But the heart is an incredibly complex organ to study in the lab, Van der Velden explains, because it beats and has blood vessels running through it. Much like the brain, that makes it difficult to duplicate.
“So, that’s the challenge. When I learned there are so many young people with congenital heart disease, it made me extra motivated to push ahead with this research. We had one of our patient days last November, when you meet the families, and at times like that it really hits home how important this research is. Heart failure isn’t something that affects only older people. Sadly, I also see many young patients whose lives are upended by this disease.”
Whole families can be the carriers of genetic heart conditions, in which they have a mutation in their DNA that can cause heart failure. At present, there are no medicines that can prevent or cure these diseases. One of the complexities is that family members with the same mutation can actually present very different clinical pictures. Where one may fall down dead from sudden cardiac arrest, another experiences only mild symptoms, lives to a ripe old age and dies from something else, like cancer. This raises a multitude of research questions about why one mutation carrier is at an elevated risk of a heart attack, while another is not.
Van der Velden’s ground-breaking research would be inconceivable without recent rapid advances in stem cell work. With these innovations to build on, Van der Velden and her team drew up a step-by-step plan for their research. First, they isolate cells from the blood of heart patients who have a mutation. Next, they convert those cells – mutations and all – into what are known as ‘induced pluripotent stem cells’, which are cells with the potential to grow into any type of cell in the human body. In the lab, the team grow the stem cells into heart muscle cells.
Besides looking at these lab-grown heart muscle cells under her microscope, Van der Velden also uses them to create those odd and intriguing strips of heart muscle. “It’s extraordinary, because it’s still a relatively new technique. It is still very expensive and you need good hands in the lab. But it’s also advancing very quickly and we are betting everything on it. It gives us a terrific model to look at how mutations change the mechanics of heart muscle tissue. And, of course, to test medications – to test if a drug works well, or has an adverse effect.”
The new method is an excellent addition to a method Van der Velden designed as part of her PhD research, which involves extracting cells from tissue removed during heart surgery. “That was an animal-free innovation, as we used postoperative waste material instead of animal cells. We use those post-op cells for strength tests looking at how the tissue behaves. One drawback of this method, though, is that you’re studying a diseased heart, whereas what you really want to know is how a healthy heart with a mutation becomes diseased over time. That’s what our new method lets us do.”
There seems to be no end to the possibilities miniature hearts offer, but personalised medicine has to be the holy grail. Van der Velden describes what this medical dream future might look like: “We would use a patient’s cells to grow twenty mini hearts in the lab. Then, we use those to test twenty medications and work out which is best for that one patient. That’s personalised therapy.”
Rosy as this future sounds, there are still quite a few steps needed to get there. “The technological advances are beyond belief, but it still takes several months to grow a miniature heart for a patient. The whole process needs to be faster, more efficient and less expensive. Still, I believe it’s possible.”
‘‘If a treatment costs one million euros per patient, you hit a wall’
For all the promise of her mini hearts, Van der Velden is also looking beyond the boundaries of her own field. “We are working with Professor Riekelt Houtkooper’s group at Amsterdam UMC. He’s studying metabolic diseases that can lead to heart conditions over time. Often, those are very unique patients for whom it makes sense to offer personalised therapies. Things like changes to diet or lifestyle. At the same time, interventions such as gene therapy are clearly advancing. That’s good, because the best way to fix a congenital condition is to correct the genetic defect.”
According to Van der Velden, these methods are all heading in the same direction. “We are in fact working towards being able to say: this drug is the best one for this group of patients.” Yet, with healthcare costs rising, won’t innovative therapies be too expensive? Van der Velden admits it’s a valid question. “Still, technologies are becoming affordable as they continue to be developed further. That’s true in other areas of medicine as well, of which the RNA vaccine for Covid-19 is an obvious example. And, with new testing methods, it will be easier to detect if a person is at risk. This will let us make more informed decisions about whom to treat, or not, thus saving on costs. It’s too expensive otherwise, and the cost of healthcare is going up fast enough as it is. If a treatment costs one million euros per patient, you hit a wall. But I do think our treatment will ultimately be affordable.”
Curious to see the miniature hearts in action? Check out this VU video.
Translation: Taalcentrum VU