Congenital arrhythmias are inherited disorders of the heart’s electrical system that can cause life-threatening rhythm disorders and sudden cardiac death. Although each condition is rare, together they affect approximately 1 in 2,000 people worldwide. For many patients, effective treatment options remain limited.

heart stem cell model

To develop better treatments, it is essential to study heart disease in models that closely reflect the biology of the human heart. Human pluripotent stem cells offer a unique opportunity in this regard.

Richard Davis, LUMC Group Leader, Associate Investigator reNEW Leidenexplains: “Pluripotent stem cells can be expanded indefinitely and coaxed into almost any cell type in the body in the lab.” Our group uses them to generate heart cells, allowing us to study arrhythmias and develop new treatments in human-relevant models. ”

In recent years, cardiac stem cell models have become increasingly complex. “Early models consisted of a monolayer of cardiomyocytes,” says Davis. “We are now creating small 3D structures containing multiple cardiac cell types. These structures are also known as cardiac microtissues and more closely mirror the human heart.

From simple cells to 3D microtissues

Using fluorescent dyes that respond to calcium signals and electrical activity, researchers can closely monitor the beating behavior of these microscopic tissues and study how drugs affect heart rhythm.

Importantly, the researchers showed that these 3D microtissues were able to predict drug-induced effects on cardiac function at a level comparable to more labor-intensive 3D heart models. At the same time, microtissues are generated in a standardized and reproducible format, making them suitable for both drug safety testing and drug discovery applications.

Scale-up through automation at Leiden Bioscience Park

The researchers, in collaboration with Ncardia (formerly Pluriomics, independent of LUMC), used robotics and machine learning pipelines to automate the generation and analysis of these cardiac microtissues. This step was essential because many advanced 3D heart models are expensive and require specialized equipment and expertise, limiting their use in large-scale drug testing.

“By combining LUMC’s deep expertise in stem cell-based heart disease modeling with Ncardia’s automation, manufacturing and analytical capabilities, we have created a highly scalable platform that incorporates human-relevant cardiac biology into early drug discovery,” said Sushant Jain, director at Ncardia. “This collaboration will help us bridge the gap between academic innovation and industrial application, enabling faster and more predictive cardiac safety testing and therapeutic discovery.”

Screened over 2,000 compounds

Use of automation platforms published in Biotechnology trendsThe research team screened more than 2,000 FDA-approved compounds in a model of catecholaminergic polymorphic ventricular tachycardia (CPVT1), a severe inherited cardiac arrhythmia. Through this large-scale screen, the researchers identified about 100 compounds that could correct abnormal heart rhythms in the model.

These compounds are currently being further studied to evaluate their potential as future treatments for patients.

Potential uses

This platform can be used for a wide range of applications. These include testing the cardiac safety of new drugs and studying the harmful effects of chemicals on human heart tissue.

This technology could also open new possibilities for patients who do not respond to standard treatments, and for whom treatment options remain limited. “Using stem cells from individual patients, we can generate personalized cardiac microtissues,” Davis says. “This brings us closer to tailoring treatments to individual patients.”

LUMC is part of the Leiden Bioscience Park, an ecosystem where companies and research institutions collaborate on biotechnology and new drug development. Here, talent, startups, businesses, and researchers collaborate every day to bring innovation to patients faster. We will improve healthcare and make the world healthier little by little.

This collaboration was supported through a Southern Netherlands Campus Grant, with additional research support at LUMC from the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW).