A new automated platform developed at Leiden University Medical Centre (LUMC) promises to accelerate the discovery and testing of heart medications, offering a potentially significant advancement in the fight against cardiovascular disease. Researchers have created a system capable of producing precise, three-dimensional human heart tissue, addressing a longstanding challenge in drug advancement – accurately modeling the complexities of the human heart. The technology,detailed in a recent publication in Trends in Biotechnology,has already identified approximately 100 compounds showing promise in treating a serious inherited heart rhythm disorder.
Table of Contents
- Inherited Heart Rhythm Disorders: A Continuing Medical Challenge
- Heart Models Built with Stem Cells
- From Simple Cells to 3D Heart Tissue
- High-Precision Heart Activity Monitoring
- Scaling Up Through Automation and Artificial Intelligence
- Screening Over 2,000 Drug Compounds
- Broad Applications and Future Outlook
Researchers at Leiden University Medical Center (LUMC) have developed a new automated platform capable of producing precise, three-dimensional heart tissue, offering a faster and more efficient way to test potential heart medications. This advancement promises to accelerate drug discovery and safety evaluations, particularly for inherited heart rhythm disorders.
Heart conditions remain a leading cause of death globally, and innovations in drug development are crucial for improving patient outcomes. The new platform aims to address a critical need for more effective and targeted therapies.
Inherited Heart Rhythm Disorders: A Continuing Medical Challenge
Inherited heart rhythm disorders, also known as genetic arrhythmias, are conditions affecting the heart’s electrical system. These disorders can lead to dangerous irregularities in heartbeat or even sudden cardiac death.
While each specific condition is relatively rare, collectively they impact approximately one in 2,000 people worldwide. Effective treatment options remain limited for many patients, highlighting the need for advanced research models to develop new therapies.
Heart Models Built with Stem Cells
To create more effective treatments, researchers emphasize the importance of studying heart disease using models that accurately reflect human heart biology. Human pluripotent stem cells offer unique possibilities in this area.
“Pluripotent stem cells can divide indefinitely and, in the lab, can be directed to become most of the cell types in the body,” explained Dr. Richard Davis, a research group leader at LUMC and researcher at reNEW Leiden. “We use them to produce heart cells that allow us to study heart rhythm disorders and develop new treatments using a model that mimics the human heart.”
From Simple Cells to 3D Heart Tissue
Stem cell-based heart models have evolved significantly in recent years. Previously, models were limited to a single layer of heart muscle cells. Now, researchers are designing small, three-dimensional structures containing multiple types of heart cells, known as cardiac microtissues.
These structures more accurately represent the complex environment of the human heart compared to traditional models.
High-Precision Heart Activity Monitoring
Using fluorescent dyes that respond to calcium signals or electrical activity, researchers can now:
Monitor the beating pattern of these cardiac tissues
Study the effects of different drugs on heart rhythm
The study demonstrated that these three-dimensional tissues can predict the effects of drugs on heart function with a level of accuracy comparable to more complex and expensive heart models.
Importantly, these tissues are produced in a standardized and reproducible manner, making them suitable for drug safety testing and the discovery of new treatments.
Scaling Up Through Automation and Artificial Intelligence
In collaboration with Ncardia (formerly Pluriomics, a spin-off company from LUMC), researchers automated the production and analysis of cardiac microtissues using:
Robotics
Machine learning systems
This step is critical, as many advanced 3D heart models require costly equipment and specialized expertise, limiting their widespread use.
“By combining LUMC’s deep expertise in modeling heart disease using stem cells with Ncardia’s capabilities in automation, manufacturing, and analysis, we’ve created a scalable platform that brings human heart biology into the early stages of drug discovery,” said Shushant Jain, a director at Ncardia.
Screening Over 2,000 Drug Compounds
Using this automated platform, the results of which were published in the journal Trends in Biotechnology, the research team screened more than 2,000 drug compounds approved by the U.S. Food and Drug Administration (FDA).
The screening focused on a model of catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1), a serious inherited heart rhythm disorder.
The large-scale study identified approximately 100 drug compounds that showed the ability to correct heart rhythm disturbances in the model.
These compounds are now undergoing further investigation to assess their potential as future treatments for patients.
Broad Applications and Future Outlook
The new platform has a wide range of potential applications, including:
Testing the cardiac safety of new drugs
Studying the harmful effects of chemicals on human heart tissue
The technology could also open new avenues for patients who do not respond to conventional treatments, a group for whom therapeutic options remain limited.
“By using stem cells taken from individual patients, we can produce patient-specific cardiac microtissues, bringing us one step closer to developing treatments tailored to each case,” Dr. Davis added.
