Imagine a typical mad scientist’s laboratory: beakers bubbling with strange fluids, sparks zapping between electrical coils. And in the center of the room, a living, beating human heart growing in a dish. It sounds like something out of a cheesy science fiction movie, but it’s happening right here in Leiden Bio Science Park. Well, not exactly. The accurate part: Leiden researchers are growing realistic heart tissues in a dish.

Roxanne Kieltyka and her research group are not mad scientists; they’re supramolecular chemists. Their focus: “chemistry beyond the molecule.” Supramolecular chemistry studies how individual molecules interact and stick together, without forming strong chemical bonds. It’s like building with LEGO bricks instead of glue. Kieltyka describes it as “the possibility to build up materials from small molecules … exploring different chemistries within them, seeing how they self-assemble, and seeing their application potential.”

Originally from Toronto, Canada, Kieltyka is now an associate professor at the Leiden Institute of Chemistry. While she has always been in the field of chemistry, supramolecular chemistry has become her main interest. “Because of the interactions that hold the molecules together, the materials are dynamic,” Kieltyka explains. “When you bring together a collective, like molecules in a group, you can do a lot with them.”

Cozy home

Indeed, these small molecules have some impressive properties, such as the ability to self-assemble. Or in the case of Kieltyka’s SUPRAHEART project, to provide a cozy home in which heart cells can assemble into structures, mimicking a real human heart.

There is a very good reason behind this mad science. Heart disease is the leading cause of deaths worldwide, so research into the prevention and treatment of heart disease is very prevalent. Fortunately, tissue models allow for research on heart cells without using living patients. Tissue models are clumps of cells, grown in a lab, that mimic the structure and function of real human cells.

Kieltyka explains the SUPRAHEART project as “seeing how we can start to build up these tissue models based on induced pluripotent stem cell-derived cardiomyocytes in supramolecular materials.” That’s a bit of a mouthful, so let’s break it down:

Induced pluripotent stem cells are cells that have been “reprogrammed” to be able to become any human cell type, be it blood, bone, or liver cells. Cardiomyocytes are the cells that form the muscles in your heart – they make your heart beat.

In summary, the SUPRAHEART project is exploring how they can use lab-grown heart cells, made from reprogrammed stem cells, to create realistic heart tissues. To achieve this, they’ll need the help of supramolecular chemistry.

Molecular Scaffolding

The cells in our body require a sturdy foundation (called the extracellular matrix) to grow and divide. To grow heart tissues in the lab, researchers typically use Matrigel, an extracellular matrix harvested from mice. However, Kieltyka believes that they can make this scaffold from scratch.

A fully synthetic scaffolding has a lot of benefits, says Kieltyka. “If you look at the composition of Matrigel, there are a lot of components – but the composition itself is undefined. If you have a fully synthetic material, it becomes chemically defined.” In other words, a synthetic material means researchers know exactly what its ingredients are. If researchers repeat an experiment, the results won’t change based on the material.

“On the other hand, you also have opportunities to modulate that material’s properties better. You can use specific chemistries and then you can start to mimic a wide range of tissues.” Kieltyka explains that biological materials come “as is,” whereas synthetic materials can be customized however you like.

There is also the matter of ethics. Matrigel comes from mouse tumours. Living mice are injected with cancer cells, and a tumour is allowed to grow before the mouse is euthanized and the tumour is harvested. “A synthetic alternative would sidestep the use of animals entirely.”

Like LEGO bricks

Kieltyka’s synthetic scaffolding requires a “basic building block” to construct the material, a single molecule of interest. This molecule is designed with very specific features. For instance, they can attach “tags” to the molecules which act as signals that tell the cells what to do.

The molecule is also self-assembling. Like LEGO bricks, they can stack together to form long strands. However, they aren’t “glued” fast together (chemically bonded); they can attach and detach without as much force. Just like LEGO is designed with studs and tubes so that they can be assembled, Kieltyka’s molecule is “pre-encoded” with regions that are designed to stick together.

The self-assembled molecular strands ultimately form a gel, a squishy substance which mimics the extracellular matrix and provides a comfortable environment for heart cells.

It’s for the SUPRAHEART project that the Kieltyka group received an ERC Proof of Concept grant of €150.000 earlier this year. The ERC Proof of Concept grant provides researchers with 12 to 18 months to put their innovative research into practice, as well as explore the commercialization of their research.

innovation as a product

The Proof-of-Concept grant also encourages researchers to commercialize their findings. This is something new to Kieltyka. “Once you move into this commercialization process, it’s thinking of your innovation as a product… it comes with a whole other range of questions that also need to be explored in the lab.”

Kieltyka and her team are still considering whether they’ll market the molecular building block itself or the gel that it forms. Either way, a lot of testing needs to be done. “A group in the future may use the material for their culture experiments under these conditions or under another set of conditions.” Like with any product, this molecular scaffolding will have to be tested thoroughly before it is released commercially to users.

But one day, this fully synthetic matrix could be available on the shelves for any researcher worldwide, offering them an efficient and ethical to way grow heart cells and advance treatments for heart disease.