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Researchers from the group of reNEW Leiden AI Richard Davis and PI Christine Mummery and the Leiden-based biotech company Ncardia have joined forces to develop a new platform that enables the automated production of 3D cardiac microtissues. Using this platform, large numbers of drugs can be tested quickly, reliably, and efficiently for their effects on the heart, supporting both drug discovery and cardiac safety testing. The platform is now published in Trends in Biotechnology,
Congenital cardiac arrhythmias are inherited disorders of the heart’s electrical system and can lead to life-threatening rhythm disturbances or sudden cardiac death. Although each condition is rare, together they affect approximately 1 in 2,000 people worldwide. For many patients, effective treatment options are still limited.
Stem cell models of the heart
To develop better therapies, it is essential to study heart diseases in models that closely reflect human heart biology. Human pluripotent stem cells offer unique opportunities in this respect.
Richard Davis, group leader at LUMC and Associate Investigator at reNEW Leiden, explains: “Pluripotent stem cells can multiply indefinitely and be directed in the laboratory into almost any cell type in the body. In our group, we use them to generate heart cells which allow us to study cardiac arrhythmias and develop new treatments in a human-relevant model.”
From simple cells to 3D microtissues
In recent years, cardiac stem cell models have become increasingly complex. “Early models consisted of a single layer of heart muscle cells,” says Davis. “Today, we create small 3D structures containing multiple cardiac cell types. These structures, also known as cardiac microtissues, more closely resemble the human heart.”
Using fluorescent dyes that respond to calcium signals or electrical activity, researchers can monitor the beating behavior of these microtissues in great detail and study how drugs influence heart rhythm.
Importantly, the researchers showed that these 3D microtissues can predict drug-induced effects on heart function at a level comparable to more labor-intensive 3D heart models. At the same time, the microtissues are generated in a standardized and reproducible format, making them suitable for both drug safety testing and drug discovery applications.
Scaling up through automation at the Leiden BioScience Park
Together with Ncardiaand analysis of these cardiac microtissues using robotics and machine-learning pipelines. This step was essential, as 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 cardiac disease modelling with Ncardia’s automation, manufacturing, and analytics capabilities, we have created a scalable platform that brings human-relevant cardiac biology into early drug discovery,” says Shushant Jain, Director at Ncardia. “This collaboration allows us to bridge the gap between academic innovation and industrial application, enabling faster and more predictive cardiac safety testing and therapeutic discovery”.
Screening more than 2,000 compounds
Using the automated platform the 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 around 100 compounds that were able to correct abnormal heart rhythms in the model.
These compounds are now being studied further to assess their potential as future therapies for patients.
Potential applications
The cells needed to construct the cardiac microtissues are also commercially available via Ncardia under the name Heart-in-a-Box. The 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 chemical substances on human heart tissue.
The technology may also open new possibilities for patients who do not respond to standard therapies, a group for whom treatment options remain limited. “Using stem cells from individual patients, we can generate personalized cardiac microtissues,” says Davis. “This brings us closer to tailoring treatments to the individual patient.”
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The collaboration was supported by the Province of Zuid-Holland through a Campus subsidy, with additional research support at LUMC from the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW).
