Bioengineered 3D human heart valve tissues with enhanced maturational properties for disease modelling and therapeutic applications [spatial transcriptomics]

Here, we develop a protocol to generate 3-dimensional human heart valve tissues from pluripotent stem cells with enhanced maturational properties closely mirroring the valve interstitial cell, resident myeloid cells and protein expression profile of native heart valves.

Importantly, bioengineered heart valves transplanted subcutaneously in rats did not calcify, highlighting potential clinical utility as a cellular therapy. In parallel, using a high-throughput 96-well platform, we demonstrate that bioengineered human heart valves can be used for modelling valve disease. Treatment with inflammatory cytokines augmented tissue passive tension and upregulated molecular markers associated with valve calcification and fibrosis.