Atrial fibrillation affects over 43 million people worldwide, yet the cells used to study it in the lab come from animals, not humans. This project aims to replace those animal cells with human heart cells grown from stem cells. The problem is that current treatments for atrial fibrillation often fail or cause severe side effects. To develop better drugs, scientists need to study human atrial cells, but they currently rely on animal models that are either too different from humans (rodents) or require ethically problematic procedures (larger animals). The gap is a reliable, human-relevant cell model that can mimic the rapid, chaotic electrical activity of a fibrillating atrium. If this research succeeds, it will give laboratories a simple, standardised way to grow mature human atrial cells in 3D clusters called spheroids. These cells could then be used to test new drugs and study the mechanisms of atrial fibrillation without using animals. Because the method relies on standard lab equipment, it can be adopted widely, reducing the number of animals used in cardiovascular research globally. This is a direct replacement for animal models in drug development and fundamental heart research—not a distant application, but a near-term tool for labs already working on atrial fibrillation.
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Atrial fibrillation (AF) affects over 43 million people worldwide, posing serious health risks like stroke, heart attack, heart failure, and death. Current treatments often fail and can have severe side effects, making it crucial to develop safer, more effective therapies. To understand AF better and create new treatments, scientists rely on animal models. However, these models have significant drawbacks. Small animals like rodents differ greatly from humans, and larger animals require complex, ethically challenging procedures. This results in the use of many animals, raising ethical concerns and highlighting the need for alternative methods. Our vision is to replace these animal models with a more accurate and ethical alternative. We propose using atrial cardiomyocytes derived from human induced pluripotent stem cells (atrial hiPSC-CM). These cells, grown in the lab, can provide a more precise representation of human atrial physiology. However, to fully replicate the conditions of AF, these cells need to be structurally and functionally matured. Our project aims to achieve this maturation by developing 3D cell clusters known as spheroids. We will grow these cells in non-adhesive microwells and use techniques such as electrical stimulation and optimised growth medium to enhance maturation. The objectives of our project are: To create and analyse 3D atrial cell clusters (spheroids) and compare their properties to traditional 2D cell cultures. To investigate how electrical stimulation and optimised culture media can enhance the maturity of these cell clusters. To evaluate if these mature cell clusters can accurately model AF when subjected to rapid electrical pacing. The success of this project will provide a more accurate and ethical method for studying AF, significantly reducing the reliance on animal testing. Our approach is simple and utilises standard laboratory equipment, ensuring it can be easily adopted by other research laboratories. Given our extensive preliminary data and the team's solid expertise in this field, we are confident in the project's success.
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