Resident cells of the myocardium: more than spectators in cardiac injury, repair and regeneration

•Cell cycle re-entry accounts for most new cardiomyocytes and endothelial cells in the adult heart.•The extracellular matrix is a key source of molecules that regulate heart cell behaviour.•Fibroblasts change their phenotype to resolve inflammation after phagocytosing apoptotic cells. Multiple resident cell types contribute to maintaining the structure and physiological function of the heart over the life course. Cardiomyocyte proliferation supports scar free regeneration in the neonatal heart following injury, but a lower rate of proliferation in the adult necessitates replacement by a collagen scar to maintain ventricular integrity. In this short review we discuss recent studies that have identified novel roles for non-myocyte resident cells and the extracellular matrix in supporting repair, as well as cardiomyocyte and vascular regeneration, following myocardial infarction.