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.
Highlights
A tissue engineered oesophagus could overcome limitations associated with oesophageal substitution
Overall preservation of ECM composition and architecture post-decellularization was reflected in the mechanical properties of the scaffold with no significant difference between native and decellularized oesophageal segments in relaxation, strength and strain at break (Supplementary Fig. 1h)
Avoiding cadaveric derived scaffolds and using synthetic polymers would have the advantage of having an off-shelf product and eliminate the potential risks of infections and organ shortage[32]
Summary
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 repopulation/maturation of constructs before transplantation, (iii) cryopreservation of bioengineered organs and (iv) in vivo pre-vascularization. While previous studies focused on the cervical oesophagus, which is mainly skeletal[17,19,20,21,22], thoracic oesophagus is almost exclusively smooth muscle[2,3,4,5,6,16] Due to these limitations, all previous attempts failed to provide an optimal approach in the use of decellularized scaffolds as suitable oesophageal substitutes[16]. Overall our approach provides a fully re-populated, structurally organized and pre-vascularized oesophageal substitute, which could become, in the near future, a novel and valid alternative for treatment of congenital or acquired oesophageal defects
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