Mini-Hearts for better treatments of inherited heart disease
BEAT-PLN is a collaboration between the University of Twente and PLaN Therapeutics that aims to develop advanced human heart-on-chip models for phospholamban (PLN) cardiomyopathy, a severe inherited heart disease. Using stem cells from patients, the consortium will create miniature beating heart tissues that closely mimic the disease in the laboratory. These “mini-hearts” will provide a powerful new tool for understanding disease mechanisms and evaluating potential treatments.
PLN cardiomyopathy is one of the most important inherited heart diseases in the Netherlands because of a founder mutation that affects many families. The disease can cause dangerous heart rhythm disturbances, progressive heart failure, and sudden cardiac death. Current treatments mainly address symptoms and do not correct the underlying cause. Animal models and conventional cell cultures only partly reflect the human disease, making it difficult to predict whether new therapies will work in patients.
The project combines patient-derived stem cell technology, tissue engineering, and organ-on-chip technology. Heart cells generated from patient stem cells will be assembled into three-dimensional beating tissues and cultured in a standardized microfluidic platform. Integrated sensors and electrical stimulation will allow researchers to measure contractility, calcium handling, rhythm disturbances, and other clinically relevant features. Potential therapies, including gene-based approaches and small molecules, will be tested directly on these human mini-hearts.
The project will deliver a validated human heart-on-chip model for PLN cardiomyopathy, standardized protocols for disease modelling and drug testing, and new insights into disease mechanisms. It will also identify which emerging therapies show the greatest promise for further development. By providing a more predictive human model, BEAT-PLN will accelerate therapy development, support personalized medicine, and contribute to reducing animal experiments in cardiovascular research.
