Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

Sebastian Sjoqvist, Philipp Jungebluth, Mei Ling Lim, Johannes C. Haag, Ylva Gustafsson, Greg Lemon, Silvia Baiguera, Miguel Angel Burguillos, Costantino Del Gaudio, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Karolina Kublickiene, Henrik Ullman, Heike Kielstein, Peter Damberg, Alessandra Bianco, Rainer Heuchel, Ying Zhao, Domenico Ribatti, Cristián IbarraBertrand Joseph, Doris A. Taylor, Paolo Macchiarini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3562
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014

Fingerprint

esophagus
Tissue Transplantation
transplantation
Scaffolds
Esophagus
rats
Rats
Tissue
Grafts
Muscle
animals
Animals
muscle fibers
Transplants
bioreactors
angiogenesis
muscle cells
Mechanical Stress
Pediatrics
patents

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)

Cite this

Sjoqvist, S., Jungebluth, P., Ling Lim, M., Haag, J. C., Gustafsson, Y., Lemon, G., ... Macchiarini, P. (2014). Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nature Communications, 5, [3562]. https://doi.org/10.1038/ncomms4562

Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. / Sjoqvist, Sebastian; Jungebluth, Philipp; Ling Lim, Mei; Haag, Johannes C.; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Angel Burguillos, Miguel; 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.

In: Nature Communications, Vol. 5, 3562, 2014.

Research output: Contribution to journalArticle

Sjoqvist, S, Jungebluth, P, Ling Lim, M, Haag, JC, Gustafsson, Y, Lemon, G, Baiguera, S, Angel Burguillos, M, Del Gaudio, C, Rodríguez, AB, Sotnichenko, A, Kublickiene, K, Ullman, H, Kielstein, H, Damberg, P, Bianco, A, Heuchel, R, Zhao, Y, Ribatti, D, Ibarra, C, Joseph, B, Taylor, DA & Macchiarini, P 2014, 'Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats', Nature Communications, vol. 5, 3562. https://doi.org/10.1038/ncomms4562
Sjoqvist S, Jungebluth P, Ling Lim M, Haag JC, Gustafsson Y, Lemon G et al. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. Nature Communications. 2014;5. 3562. https://doi.org/10.1038/ncomms4562
Sjoqvist, Sebastian ; Jungebluth, Philipp ; Ling Lim, Mei ; Haag, Johannes C. ; Gustafsson, Ylva ; Lemon, Greg ; Baiguera, Silvia ; Angel Burguillos, Miguel ; 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. / Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats. In: Nature Communications. 2014 ; Vol. 5.
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