title: Does the developing liver inhibit early lung growth in congenital diaphragmatic hernia?
abstract: It has been hypothesised that the liver induces lung hypoplasia in congenital diaphragmatic hernia (CDH) by non-compressive intrathoracic growth rather than traditional mass herniation. Utilising a co-culture system, we tested the capacity of liver cells to inhibit lung growth by contact rather than compression. Heart, liver, and lungs were microdissected from normal rat embryos (n > 20 from at least three litters) on day 13.5 of gestation. Monolayer cultures of enzymatically dispersed livers and hearts were established at the same cell density. Lung primordia were cultured in direct contact with hepatic cells or partitioned from them by a permeable polytetrafluoroethylene membrane. This permits the contributions of diffusable factors and cell contact to be distinguished. Lungs were similarly cultured in direct contact with or partitioned from cardiac cells. Lungs cultured in isolation served as further controls. Daily inspection permitted assessment of in-vitro lung growth. Growth of lungs in direct contact with hepatic cells was equivalent to that of lungs partitioned from liver cells. Lungs in direct contact with cardiac cells and lungs partitioned from cardiac cells were also not inhibited compared to lungs cultured in isolation. Early lung development is thus not inhibited by humoral or contact-mediated interactions with embryonic liver cells. Lung hypoplasia in CDH is therefore unlikely to originate from contact inhibition with the developing liver. An intrinsic pulmonary defect may better explain hypoplastic lung development in CDH.
authors.affiliation: Institute of Child Health, Alder Hey Children's Hospital, Eaton Road, Liverpool L12 2AP, UK.
authors.forename: E C
authors.initials: EC
authors.lastname: Jesudason
authors.forename: M G
authors.initials: MG
authors.lastname: Connell
authors.forename: D G
authors.initials: DG
authors.lastname: Fernig
authors.forename: D A
authors.initials: DA
authors.lastname: Lloyd
authors.forename: P D
authors.initials: PD
authors.lastname: Losty
mesh_terms: D000818:Animals; D002452:Cell Count; D018929:Cell Culture Techniques; D005260:Female; D006321:Heart / Q000196:embryology / Q000503:physiopathology; D022781:Hepatocytes / Q000201:enzymology* / Q000502:physiology; D006548:Hernia, Diaphragmatic / Q000196:embryology / Q000503:physiopathology*; D065630:Hernias, Diaphragmatic, Congenital; D008099:Liver / Q000196:embryology* / Q000503:physiopathology*; D008168:Lung / Q000002:abnormalities / Q000196:embryology* / Q000503:physiopathology*; D008171:Lung Diseases / Q000151:congenital* / Q000196:embryology / Q000503:physiopathology*; D011138:Polytetrafluoroethylene; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011138:Polytetrafluoroethylene