Transatlantic collaboration identifies key molecule for cardiac bioengineering (and regeneration?)

Our friends and collaborators in the Sinha lab in Cambridge published an exciting paper in Stem Cell Reports that reports the key role of an extracellular matrix component, fibronectin, in the maturation of cardiomyocytes seeded in 3D scaffolds together with epicardial cells (forming so-called 3D Engineered Heart Tissues, 3D-EHTs). The study involved a transatlantic collaboration with the Murry lab in Seattle, WA. We were glad to contribute to the genome editing experiments that led to the formal demonstration that fibronectin is required for the pro-maturation activity of epicardial dells.

Here are the highlights of the manuscript:

• Loss of epicardial fibronectin led to immature stem cell-derived cardiomyocytes in 3D-EHTs
• Adding recombinant fibronectin recovered the maturation effect of epicardium in 3D-EHTs
• Fibronectin is part of the epicardial-cardiomyocyte crosstalk driving myocardial maturation
• Epicardial-cardiomyocyte interactome shows key signaling pathways in cardiac development

​A previous study from the same collaborative group had identified they key ability of epicardial cells to promote cardiomyocyte maturation both in vitro and in vivo, but the mechanism remained unclear. This study identifies fibronecting as being both sufficient and necessary for this process in vitro, which opens the door to simplified and more reproducible bioengineering applications compared to adding epicardial cells.

Fibronectin may prove key to also boost cardiac remuscolarization in vivo. Indeed, the immaturity of human pluripotent-derived cardiomyocytes (hPSC-CMs) is thought to be a key driver of arrhythmic complications following their transplantation: what if a pinch of fibronectin in transplanted hPSC-CMs improved their safe engraftment and function?There promises to be a third episode of this saga..