Urbani, L;
Camilli, C;
Phylactopoulos, DE;
Crowley, C;
Natarajan, D;
Scottoni, F;
Maghsoudlou, PL;
... De Coppi, P; + view all
(2018)
Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors.
Nature Communications
, 9
, Article 4286. 10.1038/s41467-018-06385-w.
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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.
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