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| Replacement of the Trachea with Fully Bioengineered Graft in Pigs | |
Tetsuhiko Go1, Philipp Jungebluth1, Adelaide Asnaghi2, Sara Mantero2, Maria-Teresa Conconi3, Antony Hollander4, Martin Birchall4, Paolo Macchiarini1; 1General Thoracic Surgical Experimental Laboratory, Universitat de Barcelona, Barcelona, Spain; 2Department of Bioengineering, Politecnico di Milano, Milano, Italy; 3Pharmaceutical Science, University of Padua, Padua, Italy; 4Department of Cellular and Molecular Medicine, School of Medical Sciences, Bristol, United Kingdom
Methods: Non-immunogenic tracheal matrices were obtained via detergent-enzymatic method (DEM) from pig donors. MHC-unmatched animals (weighing 65±4 Kg) were divided into four groups (each, n=5) and 6 cm of their tracheas replaced with a DEM matrix alone (group I) or seeded with recipients autologous chondrocytes (group II) or epithelial cells (group III), or both (groupIV). Epithelial cells (via bronchial-epithelial biopsies) and stem cells (bone marrow aspiration) were harvested from recipients and in-vitro cultured. Stem cells were differentiated into chondrocytes using specific growth factors. Both cell types were seeded simultaneously using a novel bioreactor allowing dynamic and physiological cell culture. Pigs were observed during study period of 60 days via bronchoscopy, blood samples and biopsies. Grafts were evaluated mechanically and immunohistologically pre-implantation and post-mortem. Results: Matrices were completely covered with both chondrocytes and epithelial cells within 72 hours using the new device. Extent of seeding affected animals life time and outcome significantly (p<0.05) (group I: 11±2days; II: 29±4 days; III: 34±4 days; IV: 60±1 days). Animals died due to severe respiratory disorders (group I), grafts bacteria contamination (group II) or stenosis and anastomotic failure (group III). Group IV animals showed bronchoscopically healthy and bland covered graft surface without any collapse of the graft. No rejection signs occurred in this immunosuppression-free model. Grafts strain abilities were equal to native tracheas (tissue deformation: 211±13 vs 206±12%). Conclusion: The obtained bioengineered tracheal graft demonstrated its high potential as airway replacement. Back to 2009 Annual Meeting Back to Program Outline Back to Main Program |
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