Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
journal contributionposted on 2020-09-14, 10:44 authored by 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, Paolo De Coppi
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.