Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

• Published in: Nature communications Vol. 5; no. 1; p. 3562
• Main Authors: Sjöqvist, Sebastian, Jungebluth, Philipp, Lim, Mei Ling, Haag, Johannes C, Gustafsson, Ylva, Lemon, Greg, Baiguera, Silvia, Burguillos, Miguel Angel, Del Gaudio, Costantino, Rodríguez, Antonio Beltrán, Sotnichenko, Alexander, Kublickiene, Karolina, Ullman, Henrik, Kielstein, Heike, Damberg, Peter, Bianco, Alessandra, Heuchel, Rainer, Zhao, Ying, Ribatti, Domenico, Ibarra, Cristián, Joseph, Bertrand, Taylor, Doris A, Macchiarini, Paolo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 15.04.2014
• Subjects: Animals; Cell Differentiation; Esophagus - pathology; Esophagus - transplantation; Immunocompetence; Mesenchymal Stromal Cells; Myocytes, Smooth Muscle - pathology; Rats; Regeneration; Tissue Engineering - methods; Tissue Scaffolds
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms4562

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.