Heart valve tissues created from stem cells

A Melbourne research team, led by the Murdoch Children’s Research Institute (MCRI), has used stem cells to create lab-grown heart valve tissues that closely resemble those in the human body. Described in the journal Cell Stem Cell, their breakthrough should help advance our understanding into how human heart valves develop, mature and become damaged, accelerating regenerative approaches for repairing damaged valves in children and adults.

Heart valve disease is a major global health issue, affecting about 28 million people. The disease occurs when one or more of the heart’s four valves don’t open or close properly, disrupting blood flow. Left untreated, it may cause the heart to work harder and ultimately become life-threatening.

“Heart valve disease can be caused by developmental abnormalities, infection or age-related degeneration,” explained MCRI’s Dr Holly Voges, also an Associate Investigator at the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW). “Currently there are no treatments that can reverse the damage. Most patients depend on valve replacement surgery, which has significant limitations, including a high risk of blood clots and, for children, the likelihood of needing multiple procedures over their lifetime.

“To overcome this, our team has addressed a major challenge in heart valve biology. By creating heart valve tissues that mimic the molecular features of a human version, we can now test and advance new treatments at scale in the lab.”

The researchers also showed that the platform could model inflammatory valve disease, an underlying precursor to rheumatic heart disease (RHD). Australia has some of the highest recorded rates of RHD in the world, with this largely preventable disease disproportionately impacting Indigenous populations.

“When exposed to inflammatory proteins linked to rheumatic heart disease discovered in previous studies, we found the engineered stem cell tissues became stiffer and showed biomarkers consistent with diseased human valves,” Voges said.

MCRI Professor Enzo Porrello, also Director of the Melbourne node of reNEW, added, “Engineered stem cells have enabled us to closely recreate the complex structure of human valve tissue. In the future, this technology could be used to more accurately model valve disease and support the development of stem cell-derived replacement valves that grow and adapt with a patient.”

Image caption: Dr Holly Voges with seven-year-old Emily, who has a congenital heart defect that impacts the flow of blood between the heart and lungs.