Objective: We aimed to design and test an ex-vivo human umbilical cord (HUC) perfusion model simulating a fetal inflammatory response (FIR) during intra-amniotic infection. Study Design: A 2-chamber model was designed to accommodate 2 pieces of umbilical cord. Cord perfusion was performed with placental blood. Intra-amniotic exposure to infectious organisms was simulated by adding lipopolysaccharide to the artificial amniotic fluid (AAF) compartment. As a measure of inflammatory response, we used interleukin 8 (IL-8) concentration in AAF and plasma by enzyme-linked immunosorbent assay (ELISA). Wilcoxon signed rank test was used for statistical analysis. Results: We established a stable physiological setup. Results revealed significantly elevated plasma IL-8 concentrations (n = 6, P < .05) in the blood compartment of umbilical cords exposed to lipopolysaccharide. Concentrations within AAF were not significantly elevated (n = 6, P = .3095). Conclusion: Simulation of a FIR in an ex-vivo model of HUC perfusion under physiological conditions is possible. Further work is necessary to establish histological funisitis.
Dammann O., O’Shea T.Cytokines and perinatal brain damage. Clin Perinatol. 2008;35(4):643-663, v.
2.
Malaeb S., Dammann O.Fetal inflammatory response and brain injury in the preterm newborn. J Child Neurol.2009;24(9): 1119-1126.
3.
Romero R., Gomez R., Ghezzi F., et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol. 1998;179(1):186-193.
4.
Goldenberg RL , Hauth JC, Andrews WWIntrauterine infection and preterm delivery . N Engl J Med. 2000;342(20): 1500-1507.
5.
Gravett M., Witkin S., Haluska G., Edwards J., Cook M., Novy M.An experimental model for intraamniotic infection and preterm labor in rhesus monkeys. Am J Obstet Gynecol. 1994;171(6):1660-1667.
6.
Gomez R., Romero R., Ghezzi F., Yoon BH, Mazor M., Berry SMThe fetal inflammatory response syndrome. Am J Obstet Gynecol . 1998;179(1):194-202.
7.
Dammann O., Leviton A.Role of the fetus in perinatal infection and neonatal brain damage. Curr Opin Pediatr. 2000;12(2): 99-104.
8.
Kim CJ, Yoon BH, Romero R., et al. Umbilical arteritis and phlebitis mark different stages of the fetal inflammatory response. Am J Obstet Gynecol. 2001;185(2):496-500.
9.
Liu Y., Shaw SK, Ma S., Yang L., Luscinskas FW, Parkos CARegulation of leukocyte transmigration: cell surface interactions and signaling events. J Immunol. 2004;172(1):7-13.
10.
Koskinen K. , Vainio PJ, Smith DJ, et al. Granulocyte transmigration through the endothelium is regulated by the oxidase activity of vascular adhesion protein-1 (VAP-1). Blood. 2004;103(9):3388-3395.
11.
De Dooy J., Colpaert C., Schuerwegh A., et al. Relationship between histologic chorioamnionitis and early inflammatory variables in blood, tracheal aspirates, and endotracheal colonization in preterm infants. Pediatr Res. 2003;54(1): 113-119.
12.
Romero R., Chaiworapongsa T., Espinoza J.Micronutrients and intrauterine infection, preterm birth and the fetal inflammatory response syndrome. J Nutr. 2003;133(5 suppl 2): 1668S-1673S.
13.
Dammann O., Leviton A.Inflammatory brain damage in preterm newborns-dry numbers, wet lab, and causal inferences. Early Hum Dev. 2004;79(1):1-15.
14.
Lewalle JM, Castronovo V., Goffinet G., Foidart JMMalignant cell attachment to endothelium of ex vivo perfused human umbilical vein. Modulation by platelets, plasma and fibronectin. Thromb Res. 1991;62(4):287-298.
15.
Kolpakov V. , D’Adamo MC, Salvatore L., et al. Neutrophil derived cathepsin G induces potentially thrombogenic changes in human endothelial cells: a scanning electron microscopy study in static and dynamic conditions. Thromb Haemost. 1994;72(1):140-145.
16.
Gan L., Sjogren LS, Doroudi R., Jern S.A new computerized biomechanical perfusion model for ex vivo study of fluid mechanical forces in intact conduit vessels. J Vasc Res. 1999; 36(1):68-78.
17.
Castronovo V., Parent B., Foidart JM, et al. Perfusion of human umbilical veins. A new approach to study the interactions of circulating malignant cells with vascular wall and their modulations. Invasion Metastasis. 1988;8(6):332-350.
18.
Grosse J.Induktion von Proteinen der extrazellulären Matrix durch VEGF in der perfundierten Arterie der humanen Nabelschnur. Doctoral Thesis. Charité Berlin, Campus Benjamin Franklin. 2007.
19.
Locatelli A. , Andreani M., Ghidini A., et al. Amnioinfusion in preterm PROM: effects on amnion and cord histology. J Perinatol. 2008;28(2):97-101.
20.
Kim CJ, Yoon BH, Kim M., Park JO, Cho SY, Chi JGHistotopographic distribution of acute inflammation of the human umbilical cord. Pathol Int. 2001;51(11):861-865.
21.
Ball M., Jobe A., Polglase G., et al. High and low body temperature during the initiation of ventilation for near-term lambs. Resuscitation.2009;80(1):133-137.
22.
Piper H., Alexander J., Shukla A., et al. Real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. Pediatrics. 2006;118(3):1176-1184.
23.
Yektaei-Karin E., Moshfegh A., Lundahl J., Berggren V., Hansson L., Marchini G.The stress of birth enhances in vitro spontaneous and IL-8-induced neutrophil chemotaxis in the human newborn. Pediatr Allergy Immunol. 2007;18(8):643-651.
24.
Cornblath M. , Hawdon J., Williams A., et al. Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds. Pediatrics. 2000;105(5):1141-1145.
25.
Ranjbaran H. , Wang Y., Manes TD, et al. Heparin displaces interferon-gamma-inducible chemokines (IP-10, I-TAC, and Mig) sequestered in the vasculature and inhibits the transendothelial migration and arterial recruitment of T cells. Circulation. 2006;114(12):1293-1300.
26.
Haraldsen G. , Kvale D., Lien B., Farstad IN, Brandtzaeg P.Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human microvascular endothelial cells. J Immunol . 1996;156(7):2558-2565.
27.
D’Alquen D., Kramer BW, Seidenspinner S., et al. Activation of umbilical cord endothelial cells and fetal inflammatory response in preterm infants with chorioamnionitis and funisitis. Pediatr Res. 2005;57(2):263-269.
28.
Byrne MF, Corcoran PA, Atherton JC, et al. Stimulation of adhesion molecule expression by Helicobacter pylori and increased neutrophil adhesion to human umbilical vein endothelial cells. FEBS Lett. 2002;532(3):411-414.
29.
Lee TH, Avraham H., Lee SH, Avraham S.Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin-8 in human brain microvascular endothelial cells. J Biol Chem. 2002;277(12): 10445-10451.
30.
Craven CM, Ward K.Fetal endothelial cells express vascular cell adhesion molecule in the setting of chorioamnionitis. Am J Reprod Immunol. 2000;43(5):259-263.
31.
Hsu C., Meaddough E., Aversa K., Copel J. The role of amniotic fluid L-selectin, GRO-alpha, and interleukin-8 in the pathogenesis of intraamniotic infection. Am J Obstet Gynecol. 1998;178(3):428-432.
