Heart assembloids give researchers a new way to study heart valve disorders

A multidisciplinary team of researchers from various institutions, led by Guang Li, an associate professor at the School of Medicine's Department of Cell Biology, has developed a novel approach to study heart valve disorders. They created heart valve models using "assembloids," which are miniature, simplified versions of a human heart chamber grown on a chip the size of a postage stamp.

This innovative method allowed the team to better understand and potentially treat various heart conditions, including mitral valve prolapse (MVP), a genetic disorder affecting millions of people in the U.S.

Heart valves, unlike those of animals, have unique physiological and genetic characteristics that make it difficult to study human valve diseases using animal models. To create an accurate model, the researchers combined different types of heart cells into organoids and then grew a valve on the surface of a heart assembloid. They also incorporated mechanical forces, such as flowing medium to simulate blood, endothelial culture to mimic cells lining heart valves, and magnetized beads to replicate muscle contraction, into the model.

With this advanced model, the team was able to study four types of valve disorders, including MVP. By introducing a mutation associated with the disease, they observed signs of MVP in the developing valves. Additionally, they simulated damage caused by factors like valve calcification, cryoinjury, and complications from hypoglycemia and diabetes. The researchers identified pathways responsible for developmental problems associated with MVP and potential treatment targets.

Moving forward, the team plans to create more complex assembloids by growing them with two chambers and growing the valves inside them, closer to the structure of a real human heart.