title: Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism.
abstract: OBJECTIVE
  Necrotising enterocolitis (NEC) remains one of the primary causes of morbidity and mortality in neonates and alternative strategies are needed. Stem cells have become a therapeutic option for other intestinal diseases, which share some features with NEC. We tested the hypothesis that amniotic fluid stem (AFS) cells exerted a beneficial effect in a neonatal rat model of NEC.
  
  
  METHODS
  Rats intraperitoneally injected with AFS cells and their controls (bone marrow mesenchymal stem cells, myoblast) were analysed for survival, behaviour, bowel imaging (MRI scan), histology, bowel absorption and motility, immunofluorescence for AFS cell detection, degree of gut inflammation (myeloperoxidase and malondialdehyde), and enterocyte apoptosis and proliferation.
  
  
  RESULTS
  AFS cells integrated in the bowel wall and improved rat survival and clinical conditions, decreased NEC incidence and macroscopic gut damage, improved intestinal function, decreased bowel inflammation, increased enterocyte proliferation and reduced apoptosis. The beneficial effect was achieved via modulation of stromal cells expressing cyclooxygenase 2 in the lamina propria, as shown by survival studies using selective and non-selective cyclooxygenase 2 inhibitors. Interestingly, AFS cells differentially expressed genes of the Wnt/β-catenin pathway, which regulate intestinal epithelial stem cell function and cell migration and growth factors known to maintain gut epithelial integrity and reduce mucosal injury.
  
  
  CONCLUSIONS
  We demonstrated here for the first time that AFS cells injected in an established model of NEC improve survival, clinical status, gut structure and function. Understanding the mechanism of this effect may help us to develop new cellular or pharmacological therapies for infants with NEC.
authors.affiliation: Surgery Unit, University College London Institute of Child Health, , London, UK.
authors.forename: Augusto
authors.initials: A
authors.lastname: Zani
authors.forename: Mara
authors.initials: M
authors.lastname: Cananzi
authors.forename: Francesco
authors.initials: F
authors.lastname: Fascetti-Leon
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauriti
authors.forename: Virpi V
authors.initials: VV
authors.lastname: Smith
authors.forename: Sveva
authors.initials: S
authors.lastname: Bollini
authors.forename: Marco
authors.initials: M
authors.lastname: Ghionzoli
authors.forename: Antonello
authors.initials: A
authors.lastname: D'Arrigo
authors.forename: Michela
authors.initials: M
authors.lastname: Pozzobon
authors.forename: Martina
authors.initials: M
authors.lastname: Piccoli
authors.forename: Amy
authors.initials: A
authors.lastname: Hicks
authors.forename: Jack
authors.initials: J
authors.lastname: Wells
authors.forename: Bernard
authors.initials: B
authors.lastname: Siow
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: Colin
authors.initials: C
authors.lastname: Bishop
authors.forename: Alberta
authors.initials: A
authors.lastname: Leon
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: Agostino
authors.initials: A
authors.lastname: Pierro
authors.forename: Simon
authors.initials: S
authors.lastname: Eaton
authors.forename: Paolo
authors.initials: P
authors.lastname: De Coppi
mesh_terms: D000653:Amniotic Fluid / Q000166:cytology*; D000818:Animals; D017209:Apoptosis; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D020345:Enterocolitis, Necrotizing / Q000201:enzymology / Q000628:therapy*; D020895:Enterocytes / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007413:Intestinal Mucosa / Q000201:enzymology*; D008279:Magnetic Resonance Imaging; D051381:Rats; D012038:Regeneration / Q000502:physiology*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology*; D015996:Survival Rate
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2
keywords: EXPERIMENTAL COLITIS; GASTROINTESTINAL SURGERY; INTESTINAL STEM CELL; NECROTIZING ENTEROCOLITIS; NEONATAL GUT