1. Multi-stage bioengineering of a layered oesophagus with in vitro expanded muscle and epithelial adult progenitors
- Author
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Urbani, Luca, Camilli, Carlotta, Phylactopoulos, Demetra-Ellie, Crowley, Claire, Natarajan, Dipa, Scottoni, Federico, Maghsoudlou, Panayiotis, McCann, Conor J., Pellegata, Alessandro Filippo, Urciuolo, Anna, Deguchi, Koichi, Khalaf, Sahira, Aruta, Salvatore Ferdinando, Signorelli, Maria Cristina, Kiely, David, Hannon, Edward, Trevisan, Matteo, Wong, Rui Rachel, Baradez, Marc Olivier, Moulding, Dale, Virasami, Alex, Gjinovci, Asllan, Loukogeorgakis, Stavros, Mantero, Sara, Thapar, Nikhil, Sebire, Neil, Eaton, Simon, Lowdell, Mark, Cossu, Giulio, Bonfanti, Paola, and De Coppi, Paolo
- Subjects
Animals ,Cell Culture Techniques ,Cell Differentiation ,Child ,Child, Preschool ,Cryopreservation ,Epithelial Cells ,Esophagus ,Extracellular Matrix ,Humans ,Infant ,Infant, Newborn ,Male ,Mice, Inbred C57BL ,Mice, Transgenic ,Muscle, Skeletal ,Neural Crest ,Rats, Sprague-Dawley ,Tissue Engineering ,Tissue Scaffolds ,Genetics and Molecular Biology (all) ,ACELLULAR MATRIX ,MULTIPOTENT STEM-CELLS ,DETERGENT ENZYMATIC TREATMENT ,Inbred C57BL ,Biochemistry ,Transgenic ,Mice ,lcsh:Science ,Chemistry (all) ,Skeletal ,Multidisciplinary Sciences ,Muscle ,Science & Technology - Other Topics ,SKELETAL-MUSCLE ,Science ,SMALL-INTESTINAL SUBMUCOSA ,DOG-MODEL ,Article ,Physics and Astronomy (all) ,EXTRACELLULAR-MATRIX ,Preschool ,Science & Technology ,Newborn ,Rats ,CANINE MODEL ,BIOLOGIC SCAFFOLDS ,Biochemistry, Genetics and Molecular Biology (all) ,TISSUE ,lcsh:Q ,Sprague-Dawley - 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.
- Published
- 2018