Understanding Scarring: Scarless Fetal Wound Healing as a Model

Abstract

Scarring is a frequent unwanted consequence of full-thickness wound healing because such wounds heal via repair mechanisms as opposed to regenerative mechanisms. In certain situations, however, full-thickness wounds heal without scarring. Understanding the circumstance of scarless healing may lead to facilitation of the process. For example, in utero, early in fetal life, wounds heal by regeneration instead of repair (Larson et al., 2010). This scarless fetal wound healing occurs across species, but it is age dependent—that is, at a certain time point in embryonic development, a switch is flipped that triggers scarring. In humans, this transition occurs in the last trimester of pregnancy (Wilgus, 2007). Attempts have been made to understand the factors that early in utero allow for scarless healing. One important observation is that fetal wound healing occurs with minimal inflammation (Krummel et al., 1987). By contrast, wound healing in late pregnancy and in adults is characterized by a robust inflammatory response and scar formation. Using a well-characterized embryonic murine model in which scarless healing occurs at or before embryonic day 15 (E15) and scarring occurs at or after E18, Wulff et al. (2012, this issue) examined the potential role of mast cells in scar formation during fetal wound healing, based on evidence that mast cells are involved in fibrosis in conditions such as keloids and scleroderma. In evaluating cultured mast cells, normal skin, and wounded skin from E15 and E18 mice, the investigators found that mast cells displayed decreased numbers, maturity, and function (degranulation) in E15 skin, suggesting a role for mast cells in the promotion of scarring in E18 mice. Additional experiments investigated the results of injection of mast cell lysates from E15 and E18 mice and of mast cell–deficient mice. The resulting data further supported a role for mast cells in fibrosis in this model. The possible role of mast cells in the transition from scarless to fibrotic healing suggests a potential target in therapeutics. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to the supplementary information online .