Summary
Published in Journal of Tissue Engineering and Regenerative Medicine (2020), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Coyle, Robert C., et al. Targeting HIF‐α for robust prevascularization of human cardiac organoids
Targeting HIF‐α for robust prevascularization of human cardiac organoids
Research Overview
Prevascularized 3D microtissues deliver cells effectively for cardiac repair. This lab develops self-organizing, prevascularized human cardiac organoids by co-seeding cardiomyocytes with cardiac fibroblasts, endothelial cells, and stromal cells into agarose microwells, and hypothesized that prevascularization is driven by endogenous upregulation of the hypoxia-inducible factor pathway inside the avascular microtissue.
Treating the organoids with Molidustat — a selective prolyl hydroxylase inhibitor that stabilizes HIF-α — improved endothelial expression (CD31) by 150% ± 61%, confirming the HIF pathway as a lever for building vasculature into cardiac organoids.
Key Discoveries
- HIF-α stabilization with Molidustat improved endothelial CD31 expression by 150% ± 61%
- Cardiac organoids self-organized from cardiomyocytes, fibroblasts, endothelial and stromal cells
- Confirms endogenous HIF upregulation drives prevascularization in avascular microtissues
