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World J Gastroenterol. Dec 21, 2012; 18(47): 6900-6907
Published online Dec 21, 2012. doi: 10.3748/wjg.v18.i47.6900
Esophageal tissue engineering: A new approach for esophageal replacement
Giorgia Totonelli, Panagiotis Maghsoudlou, Jonathan M Fishman, Giuseppe Orlando, Tahera Ansari, Paul Sibbons, Martin A Birchall, Agostino Pierro, Simon Eaton, Paolo De Coppi
Giorgia Totonelli, Panagiotis Maghsoudlou, Jonathan M Fishman, Agostino Pierro, Simon Eaton, Paolo De Coppi, Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, London WC1N 1EH, United Kingdom
Jonathan M Fishman, Martin A Birchall, Ear Institute, University College London, London WC1X 8EE, United Kingdom
Giuseppe Orlando, Paolo De Coppi, Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States
Tahera Ansari, Paul Sibbons, Northwick Park Institute for Medical Research, London HA1 3UJ, United Kingdom
Martin A Birchall, Paolo De Coppi, Centre for Stem Cells and Regenerative Medicine, University College London, London WC1E 6BT, United Kingdom
Author contributions: De Coppi P designed the research; Totonelli G, Maghsoudlou P, Fishman JM, Orlando G and Ansari T wrote the initial manuscript; Sibbons P, Birchall MA, Pierro A, Eaton S and De Coppi P contributed to the analysis of the data and the discussion.
Correspondence to: Paolo De Coppi, MD, PhD, Surgery Unit, Institute of Child Health and Great Ormond Street Hospital, University College London, 30 Guilford Street, London WC1N 1EH, United Kingdom. p.decoppi@ucl.ac.uk
Telephone: +44-20-79052808 Fax: +44-20-74046181
Received: April 18, 2012
Revised: June 14, 2012
Accepted: June 28, 2012
Published online: December 21, 2012
Abstract

A number of congenital and acquired disorders require esophageal tissue replacement. Various surgical techniques, such as gastric and colonic interposition, are standards of treatment, but frequently complicated by stenosis and other problems. Regenerative medicine approaches facilitate the use of biological constructs to replace or regenerate normal tissue function. We review the literature of esophageal tissue engineering, discuss its implications, compare the methodologies that have been employed and suggest possible directions for the future. Medline, Embase, the Cochrane Library, National Research Register and ClinicalTrials.gov databases were searched with the following search terms: stem cell and esophagus, esophageal replacement, esophageal tissue engineering, esophageal substitution. Reference lists of papers identified were also examined and experts in this field contacted for further information. All full-text articles in English of all potentially relevant abstracts were reviewed. Tissue engineering has involved acellular scaffolds that were either transplanted with the aim of being repopulated by host cells or seeded prior to transplantation. When acellular scaffolds were used to replace patch and short tubular defects they allowed epithelial and partial muscular migration whereas when employed for long tubular defects the results were poor leading to an increased rate of stenosis and mortality. Stenting has been shown as an effective means to reduce stenotic changes and promote cell migration, whilst omental wrapping to induce vascularization of the construct has an uncertain benefit. Decellularized matrices have been recently suggested as the optimal choice for scaffolds, but smart polymers that will incorporate signalling to promote cell-scaffold interaction may provide a more reproducible and available solution. Results in animal models that have used seeded scaffolds strongly sug- gest that seeding of both muscle and epithelial cells on scaffolds prior to implantation is a prerequisite for complete esophageal replacement. Novel approaches need to be designed to allow for peristalsis and vascularization in the engineered esophagus. Although esophageal tissue engineering potentially offers a real alternative to conventional treatments for severe esophageal disease, important barriers remain that need to be addressed.

Keywords: Esophagus; Regenerative medicine; Tissue engineering; Scaffolds; Transplantation