Aorta on a chip

In my world, we get a lot of attention and applause when we score a goal. But as I see it, these researchers and familes who work day in day out as a team to further their research and save lives also deserve applause, attention and support. Their perseverance is truly inspiring.

Toby Alderweireld

Research into inherited heart diseases

An inherited heart disease is the main reason for sudden cardiac death among young people (under 45). In Belgium, one in three people die as a result of sudden cardiac death. An inherited heart disease has life-changing implications for as many as eight other family members on average. So, early detection, correct diagnosis and appropriate treatment are vital. Thanks to innovative research, substantial progress has already been made, but the battle hasn’t been won yet.

The aorta

The aorta is the main blood vessel from the heart to the rest of the body. When the aorta becomes too wide, a tear or dissection can occur. This condition often affects young people aged between 30 and 50. In aortic dissection (i.e. a tear) more than half of all patients die. Professor Bart Loeys discovered genetic changes in numerous new genes as the cause of these aneurysms.

The research into aortic dissection focuses on two crucial questions:

Why do people with the same genetic mutation still have different clinical outcomes?
Can we develop human in vitro aortic models in order to develop new treatments?

Prof. dr. Bart Loeys and Prof. Aline Verstraeten

What is an aortic aneurysm?

An abnormal dilation of the main artery, known as an aortic aneurysm, is a silent but extremely sneaky killer. This dilation, or aneurysm, can cause the aorta to rupture, resulting in life-threatening internal bleeding and sudden death. Current treatments aren’t able to stop the disease process, only slow it down.
An aortic aneurysm develops unnoticed and there are usually no symptoms; often it’s discovered by accident. As the aneurysm widens, the aortic wall becomes weaker and thinner, like a balloon being continually inflated. The aortic wall can then rupture, even under normal blood pressure, often resulting in sudden death.
Current treatments are unable to stop the disease process. Research teams from all over the world, as well as the team working with Prof. Bart Loeys and Prof. Aline Verstraeten, are working in close collaboration to change this. Professor Aline Verstraeten explains, "We hit a crucial hurdle, which is that there are no good human models to test out new therapies for aortic aneurysm and dissection. We currently use mouse models, but the step from mice to humans is huge." There’s clearly a need for an innovative and reliable model that enables the testing and development of new therapies for humans: for instance, organ-on-a-chip technology. This research is regarded as one of the most promising breakthrough developments for future patient care.

What exactly is an organ-on-a-chip?

An organ-on-a-chip is both very simple and very complex at the same time. It’s a combination of a computer chip and cells from a real organ. No more animal experiments, but the development of an aorta-on-a-chip, a fake aorta in other words. Professor Aline Verstraeten elaborates, "We take blood cells from a patient and turn them into stem cells, which we then cultivate into the various cell types you find in the aortic wall. After that, we bring those cell types together in a 3D structure on a 'miniature chip' and subject them to blood flow and blood pressure. Thus, we mimic functional patients and control aortas. Because we start from patient samples, the full genetic context is present, allowing personalised medicine. By comparing with an aorta-on-a-chip from a healthy control subject, you also get a clearer picture of disease mechanisms. "
Similar ‘organ-on-a-chip’ models already exist for lungs, liver and kidneys, but not yet for the aorta. "We have up to now succeeded in growing the various cell types of the aortic wall from patient stem cells. Over the next two to three years, we want to bring those together on a chip. If that works, we can try therapies that appear effective in mouse models on our aorta-on-a-chip first, before testing them in clinical trials with patients. By doing so, we develop better drugs and avoid disappointing results in clinical trials. And in time, we may be able to develop and test treatments entirely animal-free."

Aim

The ultimate aim of this research is not only to unravel the mysteries surrounding hereditary causes of sudden cardiac death, but also to develop effective treatments. Once we discover why one person becomes very ill and another doesn’t, even though they have the same genetic defect, we can develop personalised treatments. By using 'aorta-on-a-chip' models, the differences can be better investigated, in order to ultimately explore innovative solutions. Using the study of aortic stem cells, researchers aim to improve genetic predictors of clinical outcomes and gain a deeper understanding of variability. This provides an excellent target for treatments. To achieve this, 40 cell lines need to be set up. Each creation of an aorta-on-a-chip costs 20 000 euros, meaning that financial support is essential to continue this promising research into hereditary causes of sudden cardiac death and aortic dissection.

Interview Toby Alderweireld

What motivated you to join this project on inherited heart diseases?
Toby: I got to know about the project as well as Aurélien's parents, Romain and Ludivine, through a contact. Aurélien has Marfan syndrome, which is one of these inherited heart diseases, and in this case, there is no cure. After talking to the people from UZA foundation, an organisation which supports clinical scientific projects of UZA and UAntwerp, I also met Professor Bart Loeys, who explained to me about the research he and his research team are doing into this syndrome, among other things. What they are accomplishing is remarkable and offers hope.
The drive and commitment of researchers like Bart, as well as Romain and Ludivine, convinced me that maybe I could help here, if only by highlighting this rare disease and the research. It’s really admirable to see how they, researchers and families, work as a tight team, pushing on every day in silence and with such dedication, achieving incredible things that no one knows about.
In my world, we get a lot of attention and applause when we score a goal or win an award. You’re then so proud of that and it gives you a boost. But as I see it, these researchers and families who work day in and day out as a team to further their research and save lives also deserve applause, attention and support. Their perseverance is truly inspiring.
Your name differs by one letter, did that play a role too?
Toby: That was definitely a good start! And of course it caught my attention. But what was most important for me was the story of Aurélien: Marfan syndrome. The respect for what his parents had already accomplished to publicise this, the incredible research they had already done themselves, their discoveries that medical professionals could take further, the efforts they made to support research.
Their commitment and dedication are of course for their son Aurélien, just as we would do the same for our children, but it’s also actually for thousands of others. This gives me this sense of being connected.

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