Study reveals role of hyaluronic acid in human heart development
Assistant Professor Keisuke Ishihara’s lab has released a new preprint that sheds light on the development of human cardioids, which are lab-made miniature heart tissue. This project was made in collaboration with Sasha Mendjan’s lab at the Institute of Molecular Biotechnology in Austria.
In the test tube, human cardioids develop into beating cardiac chambers. These cardiac organoids are miniature, 3D structures grown in the lab from stem cells and mimic the human heart. But how does a ball of stem cells turn into a hollow chamber and begin beating? Hyaluronic acid plays a key role in the form, fate and function of human heart development.
Hyaluronic acid is commonly used in skincare products like lip fillers, owing to its gel-like material properties. The study revealed the hollow chambers of miniature hearts are filled with hyaluronic acid. In fact, cells produce hyaluronic acid and surround themselves with this gel-like material, known as the extracellular matrix. Hyaluronic acid creates outward pressure to sculpt the chambers of the heart.
Beyond form, hyaluronic acid is also essential for cells to become heart muscles and begin beating.
“After these mini hearts form chambers, it only takes them another two days to start beating. It’s a remarkably rapid process, and we think the cardioids are modeling the first heart beats in human development,” Ishihara said.
When Ishihara and his team dissolved the hyaluronic acid, the miniature hearts stopped beating. Additional experiments uncovered how hyaluronic acid creates a mechanical environment that allows the cardioids to beat.
“I think the extracellular matrix is often overlooked in development,” Ishihara said. “This is one of the first examples in lab-grown organs where the cells produce a single extracellular matrix component that does so many different things. Cell-synthesized matrices open new approaches for organ engineering.”
Ishihara and his team are already beginning a new project focused on engineering cells to make hyaluronic acid. They plan to continue to explore the function of the extracellular matrix in organ development and tissue engineering.
Read the complete research article: Jahnel et al. (2026). “Hyaluronan Underlies the Emergence of Form, Fate, and Function in Human Cardioids.” bioRxiv.