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

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.

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-1beta 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.

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.

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.