Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape

Abstract

Macrophages necessary for heart regeneration Heart regeneration in salamanders is dependent on the activation of immune cells. James Godwin of The Jackson Laboratory and MDI Biological Laboratory in the US and colleagues depleted all major organs of a group of Mexican salamanders of macrophages, an immune cell responsible for removing cellular debris. They then injured the salamanders’ heart wall with a liquid nitrogen-cooled probe. Unlike adult mammals, zebrafish and salamanders can normally regenerate their hearts after injury. The team found that macrophage-depleted salamanders were unable to regenerate their hearts compared to a control group. Macrophage depletion led to the formation of a permanent fibrotic extracellular matrix scar. But it did not affect the proliferation of heart muscle cells, indicating that their function is not sufficient to prevent the progression of injury toward fibrosis instead of regeneration.