Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors

Luca Urbani, Carlotta Camilli, Demetra-Ellie Phylactopoulos, Claire Crowley, Dipa Natarajan, Federico Scottoni, Panayiotis Maghsoudlou, Conor J. McCann, Alessandro Filippo Pellegata, Anna Urciuolo, Koichi Deguchi, Sahira Khalaf, Salvatore Ferdinando Aruta, Maria Cristina Signorelli, David Kiely, Edward Hannon, Matteo Trevisan, Rui Rachel Wong, Marc Olivier Baradez, Dale Moulding, Alex Virasami, Asllan Gjinovci, Stavros Loukogeorgakis, Sara Mantero, Nikhil Thapar, Neil Sebire, Simon Eaton, Mark Lowdell, Giulio Cossu, Paola Bonfanti () and Paolo De Coppi ()
Additional contact information
Luca Urbani: Great Ormond Street Institute of Child Health, University College of London
Carlotta Camilli: Great Ormond Street Institute of Child Health, University College of London
Demetra-Ellie Phylactopoulos: Great Ormond Street Institute of Child Health, University College of London
Claire Crowley: Great Ormond Street Institute of Child Health, University College of London
Dipa Natarajan: Great Ormond Street Institute of Child Health, University College of London
Federico Scottoni: Great Ormond Street Institute of Child Health, University College of London
Panayiotis Maghsoudlou: Great Ormond Street Institute of Child Health, University College of London
Conor J. McCann: Great Ormond Street Institute of Child Health, University College of London
Alessandro Filippo Pellegata: Great Ormond Street Institute of Child Health, University College of London
Anna Urciuolo: Great Ormond Street Institute of Child Health, University College of London
Koichi Deguchi: Great Ormond Street Institute of Child Health, University College of London
Sahira Khalaf: Great Ormond Street Institute of Child Health, University College of London
Salvatore Ferdinando Aruta: Great Ormond Street Institute of Child Health, University College of London
Maria Cristina Signorelli: Great Ormond Street Institute of Child Health, University College of London
David Kiely: Great Ormond Street Institute of Child Health, University College of London
Edward Hannon: Great Ormond Street Institute of Child Health, University College of London
Matteo Trevisan: Great Ormond Street Institute of Child Health, University College of London
Rui Rachel Wong: Great Ormond Street Institute of Child Health, University College of London
Marc Olivier Baradez: Cell and Gene Therapy Catapult
Dale Moulding: Great Ormond Street Institute of Child Health, University College of London
Alex Virasami: University College of London
Asllan Gjinovci: Great Ormond Street Institute of Child Health, University College of London
Stavros Loukogeorgakis: Great Ormond Street Institute of Child Health, University College of London
Sara Mantero: Department of Chemistry, Materials and Chemical Engineering “Giulio Natta”
Nikhil Thapar: Great Ormond Street Institute of Child Health, University College of London
Neil Sebire: Great Ormond Street Institute of Child Health, University College of London
Simon Eaton: Great Ormond Street Institute of Child Health, University College of London
Mark Lowdell: Royal Free London NHS FT & UCL
Giulio Cossu: University of Manchester
Paola Bonfanti: Great Ormond Street Institute of Child Health, University College of London
Paolo De Coppi: Great Ormond Street Institute of Child Health, University College of London

Nature Communications, 2018, vol. 9, issue 1, 1-16

Abstract: Abstract A tissue engineered oesophagus could overcome limitations associated with oesophageal substitution. Combining decellularized scaffolds with patient-derived cells shows promise for regeneration of tissue defects. In this proof-of-principle study, a two-stage approach for generation of a bio-artificial oesophageal graft addresses some major challenges in organ engineering, namely: (i) development of multi-strata tubular structures, (ii) appropriate re-population/maturation of constructs before transplantation, (iii) cryopreservation of bio-engineered organs and (iv) in vivo pre-vascularization. The graft comprises decellularized rat oesophagus homogeneously re-populated with mesoangioblasts and fibroblasts for the muscle layer. The oesophageal muscle reaches organised maturation after dynamic culture in a bioreactor and functional integration with neural crest stem cells. Grafts are pre-vascularised in vivo in the omentum prior to mucosa reconstitution with expanded epithelial progenitors. Overall, our optimised two-stage approach produces a fully re-populated, structurally organized and pre-vascularized oesophageal substitute, which could become an alternative to current oesophageal substitutes.

Date: 2018
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DOI: 10.1038/s41467-018-06385-w

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