Age-dependent recruitment of neutrophils by fetal endothelial cells: implications in scarless wound healing

Purpose: Fetal dermal wounds heal with minimal inflammation and absent fibrosis. Later in gestation, a transition to adult-like healing with marked inflammation and scarring is observed. Interaction with endothelial cells (ECs) is imperative for leukocyte transmigration, a critical step in the inflammatory cascade. This study was embarked upon to determine if gestational age-dependent differences in EC function modulate changes in inflammatory response and correlate with the healing phenotype. Methods: Fetal porcine ECs were harvested at days 65 (mid gestation), 85 (late gestation), and 100 (near-term) (term = 115 days). Confluent monolayers were activated with IL-1β at 10 and 100 ng/mL and exposed to adult neutrophils under static (n = 4 per group) and continuous flow (n = 6 per group) conditions. Neutrophil-endothelial interaction was quantified and compared using analysis of variance. Results: Under static conditions, the lower cytokine dose elicited maximal neutrophil recruitment in later-gestation ECs, while midgestation ECs required higher stimulation. Midgestation ECs recruited significantly less neutrophils than later gestation ECs at both cytokine concentrations under flow conditions. Conclusion: There is a gestational age-dependent variation in neutrophil recruitment by fetal ECs. With minimal stimulation, later-gestation ECs actively recruit neutrophils, whereas midgestation ECs do not. These findings correlate with the transition period to adult-like healing, supporting the potential role of fetal ECs in scarless healing.