Filipa Simões - Cardiac Sciences / Development & Cell Biology - 'Decoding spatial heterogeneity in the regenerating heart'

Myocardial infarction (MI) causes permanent heart tissue loss in adult mammals. Following an MI, the injured heart recruits a significant number of monocyte-derived macrophages, essential immune cells that play critical roles in both scar formation and tissue regeneration. However, we still have limited understanding of the specific factors influencing distinct macrophage functions within the damaged heart. This project aims to shed light on how macrophage heterogeneity is linked to their spatial distribution across the heart and how, in turn, this distribution shapes macrophage identity and function. Despite their vital roles in cardiac repair, the intricate local environmental cues and cell-cell interactions governing the diverse roles of macrophages in this context have not been fully deciphered. By comprehending the regenerative microenvironment, where the innate immune response persists while still supporting regeneration, and by targeting macrophage-induced pro-fibrotic pathways, we may develop therapeutic strategies that harness pro-regenerative responses in the injured mammalian heart.