Mammalian cardiac regeneration: how many cell types are required?

Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration. Nat. Biotechnol. 37: 895–906 (2019)

Experimental cell therapies to treat the damaged heart often consider a single cell type (normally a cardiac progenitor or a multipotent stem cell) to substitute dead or damaged myocardium for a new, functional one. It is however, less frequent to discover approaches in which the combination of more than one cell type is proposed to sustain effective cardiac substitutive therapies. In this recent paper, Bargehr and colleagues show that co-culture of pluripotent stem cell-derived cells and immature cardiomyocytes strongly improves cardiac muscle proliferation first, then structural and functional maturation. Neovascularization of graft tissues is also fostered. The authors use engineered heart tissue constructs in vitro to test the effects of this cell-to-cell interaction and then transplant this same tissue constructs to infarcted athymic rat hearts. Together, these results suggest epicardial cells are a suitable cell adjuvant for cardiac muscle cells in the context of advanced therapies to treat the damaged heart.