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Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

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Listed:
  • Sebastian Sjöqvist

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Philipp Jungebluth

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Mei Ling Lim

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Johannes C. Haag

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Ylva Gustafsson

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Greg Lemon

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86)

  • Silvia Baiguera

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86)

  • Miguel Angel Burguillos

    (Cancer Centrum Karolinska, Karolinska Institutet)

  • Costantino Del Gaudio

    (Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome)

  • Antonio Beltrán Rodríguez

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

  • Alexander Sotnichenko

    (International Scientific-Research Clinical and Educational Center of Regenerative Medicine, Kuban State Medical University)

  • Karolina Kublickiene

    (Center for Gender Medicine, Karolinska Institutet
    Intervention and Technology (CLINTEC), Karolinska Institutet)

  • Henrik Ullman

    (Karolinska Institutet)

  • Heike Kielstein

    (Faculty of Medicine, Martin Luther University Halle-Wittenberg)

  • Peter Damberg

    (Intervention and Technology (CLINTEC) Karolinska Institutet)

  • Alessandra Bianco

    (Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome)

  • Rainer Heuchel

    (Intervention and Technology (CLINTEC), Karolinska Institutet
    Center of Biosciences, Karolinska Institutet)

  • Ying Zhao

    (Intervention and Technology (CLINTEC), Karolinska Institutet
    Center of Biosciences, Karolinska Institutet)

  • Domenico Ribatti

    (Neurosciences and Sensory Organs, University of Bari Medical School, National Cancer Institute ‘Giovanni Paolo II’)

  • Cristián Ibarra

    (Karolinska Institutet)

  • Bertrand Joseph

    (Cancer Centrum Karolinska, Karolinska Institutet)

  • Doris A. Taylor

    (Texas Heart Institute, Center for Regenerative Medicine)

  • Paolo Macchiarini

    (Advanced Center for Translational Regenerative Medicine (ACTREM), Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86
    Nose and Throat, Karolinska University Hospital)

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.

Suggested Citation

  • Sebastian Sjöqvist & Philipp Jungebluth & Mei Ling Lim & Johannes C. Haag & Ylva Gustafsson & Greg Lemon & Silvia Baiguera & Miguel Angel Burguillos & Costantino Del Gaudio & Antonio Beltrán Rodríguez, 2014. "Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats," Nature Communications, Nature, vol. 5(1), pages 1-15, May.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4562
    DOI: 10.1038/ncomms4562
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