Mature human iPSC-derived atrial cardiomyocytes to replace animals in the study of atrial fibrillation

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.