title: 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.
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Sjöqvist
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Philipp
authors.initials: P
authors.lastname: Jungebluth
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Lim
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Haag
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Gustafsson
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden.
authors.forename: Greg
authors.initials: G
authors.lastname: Lemon
authors.affiliation: Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden.
authors.forename: Silvia
authors.initials: S
authors.lastname: Baiguera
authors.affiliation: Cancer Centrum Karolinska, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Burguillos
authors.affiliation: Department of Industrial Engineering, Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome, Rome 00133, Italy.
authors.forename: Costantino
authors.initials: C
authors.lastname: Del Gaudio
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Antonio Beltrán
authors.initials: AB
authors.lastname: Rodríguez
authors.affiliation: International Scientific-Research Clinical and Educational Center of Regenerative Medicine, Kuban State Medical University, Krasnodar 350040, Russian Federation.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sotnichenko
authors.affiliation: 1] Center for Gender Medicine, Karolinska Institutet, SE-141 86 Stockholm, Sweden [2] Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Kublickiene
authors.affiliation: Department of Neuroscience, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullman
authors.affiliation: Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, 06108 Halle (Saale), Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Kielstein
authors.affiliation: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC) Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Damberg
authors.affiliation: Department of Industrial Engineering, Intrauniversitary Consortium for Material Science and Technology (INSTM) Research Unit Tor Vergata, University of Rome, Rome 00133, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bianco
authors.affiliation: 1] Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden [2] Center of Biosciences, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Rainer
authors.initials: R
authors.lastname: Heuchel
authors.affiliation: 1] Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86 Stockholm, Sweden [2] Center of Biosciences, Karolinska Institutet, SE-141 86 Stockholm, Sweden.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, National Cancer Institute 'Giovanni Paolo II', Bari 70121, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Cristián
authors.initials: C
authors.lastname: Ibarra
authors.affiliation: Cancer Centrum Karolinska, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Joseph
authors.affiliation: Texas Heart Institute, Center for Regenerative Medicine, Houston, Texas 770-30, USA.
authors.forename: Doris A
authors.initials: DA
authors.lastname: Taylor
authors.affiliation: 1] Advanced Center for Translational Regenerative Medicine (ACTREM), Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE-141 86, Stockholm, Sweden [2] Division of Ear, Nose and Throat, Karolinska University Hospital, SE-141 86 Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Macchiarini
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D004947:Esophagus / Q000473:pathology / Q000637:transplantation*; D007121:Immunocompetence; D059630:Mesenchymal Stem Cells; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D051381:Rats; D012038:Regeneration; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
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