Article Text

other Versions

PDF
Original article
Amniotic fluid stem cells improve survival and enhance repair of damaged intestine in necrotising enterocolitis via a COX-2 dependent mechanism
  1. Augusto Zani1,
  2. Mara Cananzi1,
  3. Francesco Fascetti-Leon1,
  4. Giuseppe Lauriti1,
  5. Virpi V Smith2,
  6. Sveva Bollini1,
  7. Marco Ghionzoli1,
  8. Antonello D'Arrigo3,
  9. Michela Pozzobon4,
  10. Martina Piccoli4,
  11. Amy Hicks5,
  12. Jack Wells6,
  13. Bernard Siow6,
  14. Neil J Sebire2,
  15. Colin Bishop5,
  16. Alberta Leon3,
  17. Anthony Atala5,
  18. Mark F Lythgoe6,
  19. Agostino Pierro1,
  20. Simon Eaton1,
  21. Paolo De Coppi1
  1. 1Surgery Unit, University College London Institute of Child Health, London, UK
  2. 2Department of Histopathology, Great Ormond Street Hospital for Children, London, UK
  3. 3Research & Innovation S.p.A., Padova, Italy
  4. 4Laboratory of Oncohematology, Department of Pediatrics, University of Padova, and Fondazione Città della Speranza, Padova, Italy
  5. 5Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, North Carolina, USA
  6. 6Division of Medicine, UCL Centre for Advanced Biomedical Imaging, Institute of Child Health, University College London, London, UK
  1. Correspondence to Dr Paolo De Coppi and Dr Simon Eaton, Surgery Unit, University College London Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK; p.decoppi{at}ucl.ac.uk and s.eaton{at}ucl.ac.uk

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.

Design 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.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles