Fibroblast Lineage Switching as the Developmental Origin of Scarring and Target for Regenerative Healing

The document reviews the role of fibroblast lineage switching in the transition from regenerative healing to scarring, focusing on differences between fetal and adult wound healing. Fetal skin heals without scarring due to unique fibroblast lineages, such as Engrailed-1-negative fibroblasts (ENFs), which support regenerative repair, while Engrailed-1-positive fibroblasts (EPFs) contribute to scarring in later development. Key factors include distinct extracellular matrix compositions, lower inflammatory responses, and specific cytokine profiles in fetal wounds. Understanding these mechanisms could lead to strategies for reprogramming adult fibroblasts to achieve scar-free healing by mimicking fetal conditions.