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-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. 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.
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-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. 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.
Authors: Swathi Balaji; Carey L Watson; Rajeev Ranjan; Alice King; Paul L Bollyky; Sundeep G Keswani Journal: Adv Wound Care (New Rochelle) Date: 2015-11-01 Impact factor: 4.730
Authors: Michael S Hu; Mimi R Borrelli; Wan Xing Hong; Samir Malhotra; Alexander T M Cheung; Ryan C Ransom; Robert C Rennert; Shane D Morrison; H Peter Lorenz; Michael T Longaker Journal: Organogenesis Date: 2018-02-15 Impact factor: 2.500
Authors: Claudia Nussbaum; Anna Gloning; Monika Pruenster; David Frommhold; Susanne Bierschenk; Orsolya Genzel-Boroviczény; Ulrich H von Andrian; Elizabeth Quackenbush; Markus Sperandio Journal: J Leukoc Biol Date: 2012-12-11 Impact factor: 4.962
Authors: Michael S Hu; Zeshaan N Maan; Jen-Chieh Wu; Robert C Rennert; Wan Xing Hong; Tiffany S Lai; Alexander T M Cheung; Graham G Walmsley; Michael T Chung; Adrian McArdle; Michael T Longaker; H Peter Lorenz Journal: Ann Biomed Eng Date: 2014-05-01 Impact factor: 3.934