Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Urbani, Luca; Camilli, Carlotta; Phylactopoulos, Demetra-Ellie; Crowley, Claire; Natarajan, Dipa; Scottoni, Federico; Maghsoudlou, Panayiotis; McCann, Conor; Pellegata, Alessandro; Urciuolo, Anna; Deguchi, Koichi; Khalaf, Sahira; Aruta, Salvatore Ferdinando; Signorelli, Maria; Kiely, David; Hannon, Edward; Trevisan, Matteo; Wong, Rui; Baradez, Marc; Moulding, Dale; Virasami, Alex; Gjinovci, Asllan; Loukogeorgakis, Stavros; Mantero, Sara; Thapar, Nikhil; Sebire, Neil; Eaton, Simon; Lowdell, Mark; Cossu, Giulio; Bonfanti, Paola; De Coppi, Paolo;
• Is Part Of: Nature communications. Volume 9:Issue 1(2018)
• Page Start: 1
• Page End: 16
• Publication Date: 2018-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-018-06385-w
• Languages: English
• ISSNs: 2041-1723

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. Combining decellularised scaffolds with patient-derived cells holds promise for bioengineering of functional tissues. Here the authors develop a two-stage approach to engineer an oesophageal graft that retains the structural organisation of native oesophagus.