Author:

Keywords:

Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, DETERGENT ENZYMATIC TREATMENT, SMALL-INTESTINAL SUBMUCOSA, MULTIPOTENT STEM-CELLS, EXTRACELLULAR-MATRIX, ACELLULAR MATRIX, SKELETAL-MUSCLE, CANINE MODEL, BIOLOGIC SCAFFOLDS, DOG-MODEL, TISSUE, 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

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.