Camilli, Carlotta; (2018) Development of a bioengineered oesophagus as a novel therapy for oesophageal atresia. Doctoral thesis (Ph.D), UCL (University College London).

Abstract

A tissue-engineered oesophagus could overcome the serious limitations associated with current oesophageal replacements and become a concrete therapeutic option for paediatric patients affected by long-gap oesophageal atresia or adults suffering from oesophageal cancer. Despite promising advances have been made in the field of “whole-organ” bioengineering, no efficient oesophageal substitutes are available so far. Combining decellularized scaffolds with autologous cells showed optimistic results in the regeneration of tissue defects. Thus, the purpose of my research was to generate in vitro the oesophageal muscularis externa, a layer of the oesophagus composed of muscle and nervous tissues. In this proof-of-principle study, some of the major challenges of organ engineering have been addressed: i) ideal sources of muscle and neuronal precursors have been selected; ii) appropriate repopulation and maturation of the oesophageal graft have been achieved recreating ex-vivo the optimal environment for cell growth and differentiation; iii) construct maturation and cell survival have been tested in vivo in a murine model. A cell tracking system was also fine-tuned as a valuable tool for monitoring cell migration throughout the scaffold during the culture time. Overall, the approach reported in this PhD thesis provided a fully repopulated and vascularized oesophageal construct, which in the near future could become a novel alternative for the treatment of long-gap oesophageal atresia or other oesophageal pathological conditions.

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