Cardiovascular diseases are the leading cause of death around the world. Each of us probably knows of a relative or friend who has suffered from a heart-related condition. The likelihood of developing cardiovascular disease increases with age; however, the underlying causes are not fully understood, due in part to the absence of appropriate human-based models to study. AstroCardia is aiming to change that. The project is a collaboration between five Belgian organizations – Space Applications Services, the Belgian Nuclear Research Center (SCK CEN), QbD Group, BIO INX, and Antleron – which are working together to study cardiovascular aging using a model known as a heart-on-a-chip.
A miniature heart
The heart construct itself is a tiny cluster of cells roughly in the shape of a sphere, created using 3D bioprinting and composed of three main cell types. First are cardiomyocytes, which are the cells that make up the heart’s muscles, enabling it to beat on its own. Second are endothelial cells, which make up the blood vessels. And then third are the cardiac fibroblasts, which helps in the structural stability of the organ. The chip will also contain a vascular bed, meaning that there will be blood vessels to enable the supply of nutrients and oxygen to the cells. “The chip creates the environment for the heart to function,” explains SCK CEN project leader Dr. Kevin Tabury. “We then introduce mechanical and electrical stimuli to synchronize the whole beating heart construct. This is really a perfect example of the future in healthcare.”
Martijn Reniers, Chief Innovation Officer of QbD Group, explains the vision of the five project partners: “Together, we are creating a model that could be used for personalized medicine in the future. The heart-on-a-chip that we create can be generated either from embryonic stem cells or from induced pluripotent stem cells derived from individual patients, which is ideal if you want to develop personalized medicines.”
“Using this model, we could see what kind of therapy would be most appropriate for a patient as a preventive measure against cardiovascular diseases,” says Tabury. “But if a patient has a disease that is already in an advanced stage, we could also test which drugs or treatments would be best for them. We really want to provide solutions for this worldwide medical need. Projects like this have the potential to greatly improve the quality of life of millions of people suffering from cardiovascular diseases.”
Space: a harsh environment
Heart-on-a-chip models have been developed before, but AstroCardia will be the first group to run experiments with them in space. So why are they shooting for the stars? “Space has a unique environment that we cannot replicate on Earth,” Tabury explains. “We’ve seen with astronauts on the ISS that there is an acceleration of cardiac aging about twenty times faster than on Earth. Research in this environment will allow us to create more accurate models of accelerated aging.”
“By running our study on the ISS, we will essentially be ‘speeding up time’, giving us the unique opportunity to obtain research results that we simply couldn’t obtain in the same duration down on Earth.” – Kevin Tabury
The hyper-aging that occurs in space is due to two main factors: microgravity and radiation. “Microgravity renders the heart and muscles less efficient because they don’t need to be as active as on Earth,” says Tabury. “And then radiation in chronic low doses has an impact on inflammation and DNA damage. By running our study on the ISS, we will essentially be ‘speeding up time’, giving us the unique opportunity to obtain research results that we simply couldn’t obtain in the same duration down on Earth.”
The initial experiments will be run for six weeks as a proof-of-concept to ensure that AstroCardia’s unique model works as expected. If all goes well, a new series of experiments will subsequently take place, this time for a longer period. The heart constructs have to date been successfully maintained in the SCK CEN laboratories for at least two months, and with the addition of a vascularized environment within the chip, their lifespan is expected to extend even further.
A collaborative moonshot
This project could not happen without the specialties of each of the contributing partners. SCK CEN has developed and grown the cell lines, and contributed its expertise on the interface of biology and space; BIO INX has bioprinted the vascular system within the microfluidic canals of the chip; Antleron has created the cassette, which will house the heart-on-a-chip and the nutritional media to feed the cells; QbD Group will make sure the materials are consistent and ensure validation of the manufacturing and testing process; and Space Application Services will handle transporting the hearts-on-a-chip to the ISS.
“Space is becoming more and more accessible, so this is an opportunity to do some groundbreaking research.” – Martijn Reniers
The collaboration began as a conversation between SCK CEN and Space Application Services, says Tabury: “The Belgian Nuclear Research Center has a long-lasting research expertise in space research as well as the cardiovascular system. We already knew Hilde Stenuit from Space Application Services, and so together we came up with the idea that evolved into this project.”
When QbD Group was later approached by Space Application Services, it was immediately clear to the company that the project was special with a huge potential for a positive impact on healthcare. “Space is becoming more and more accessible, so this is an opportunity to do some groundbreaking research,” says Reniers. “With the addition of BIO INX to the team, we have now formed a strong consortium that over the next years is going to do some really amazing things.”
The Flemish healthtech cluster MEDVIA – which assesses projects for funding by VLAIO – was the final piece of the puzzle, together with Flanders Space, getting AstroCardia off the ground and into the sky with project funding. “VLAIO [Flanders Innovation & Entrepreneurship, ed.] saw promise in the project as it relates to not only space but also healthcare,” Reniers comments. “So together with MEDVIA we created a VLAIO project proposal for this first-of-its-kind intercluster project (Flanders Space and MEDVIA).”
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This project represents a lot of firsts: the first Belgian collaboration of its kind, the first human-derived heart model to study the molecular basis of aging, and the first heart-on-a-chip to be studied in space. But the heart of the project is the willingness of these different innovators to work together to reach for the stars and improve the future of healthcare. As Reniers reflects: “This project will show that there is a platform that can help you in gathering data in ways we had not thought possible before. And once we can establish that, I think the sky is the limit.”