Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

Abstract

A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi.

Tissue Engineering Functional Gastrointestinal Regions: The Importance of Stem and Progenitor Cells

“…Epithelium, nerve, and muscle were identified in the graft. No original donor cells were identified suggesting ingrowth of adjacent cells (Sjoqvist et al 2014).…”

Tissue Engineering of Esophagus

“…Thus, this tissue-engineered esophageal scaffold was considered as a significant step toward the clinical application of bioengineered esophagi [66].…”

Translational Animal Models for Regenerative Medicine Research

“…More recently, tissue-engineered small intestine, stomach, large intestine, and esophagus in rats [73] have been successfully formed from syngeneic cells and employed for rescue in small-animal models (rats and mice) [73,74]. Similar studies were attempted in a large-animal model using resected short segments of jejunum or stomach from six-week-old Yorkshire swine [75].…”