Human iPSC-Derived Heart Assembloids Reproduce Valve Development and Disease

A collaborative team of researchers from the University of Pittsburgh School of Medicine and other institutions have developed a postage stamp-sized chip to model heart valve disorders using human-induced pluripotent stem cells (iPSCs). Led by Guang Li, PhD, the scientists created heart valve-like assembloids from iPSCs, which are derived from adult cells and can differentiate into various cell types, including heart cells.

To create a functional model, Li and his colleagues, including bioengineering experts Lance Davidson, PhD, and Si-Yang Zhen, PhD, incorporated mechanical forces, fluid dynamics, and other factors to replicate the environment of a real heart. They grew a valve on the surface of a heart assembloid and exposed it to various conditions, simulating blood flow, endothelial cells, and muscle contractions, to observe the development of four types of valve disorders, such as mitral valve prolapse (MVP).

The researchers found that introducing a mutation associated with MVP caused the developing valves to exhibit characteristics of the disease. They also studied other conditions like valve calcification, cryo-injury, and complications from hypoglycemia and diabetes, enabling them to identify pathways responsible for the development issues associated with MVP. Furthermore, Li plans to expand his assembloids by growing heart valves inside chambers, providing a more accurate representation of a human heart.