S.C. Dickinson, A.P. Hollander, S. Mantero, M.T. Conconi, M.A. Birchall, P. Macchiarini

The loss of a normal airway is devastating due to a lack of effective treatment methods for repairing large defects. However tissue engineering of an airway using a patient's own cells would create a complete, immunotolerant airway substitute. We therefore developed methods to bioengineer a tubular tracheal replacement and assessed the application of this technology in a patient with end-stage airway disease due to tuberculosis.

In order to generate the new tissue engineered organ, a tracheal segment was retrieved from a human organ donor and the tissue was completely decellularised using detergents and enzymes to prevent subsequent immune rejection. Autologous epithelial cells and stem cell-derived chondrocytes were isolated from the recipient and expanded and characterised in the laboratory. The cells were seeded onto the donor matrix using a novel bioreactor system designed to allow the co-culturing of different cell types, optimal nutrient transfer and three-dimensional maturation. The graft was then used to replace the recipient's left main bronchus.

The transplanted organ immediately provided the recipient with a fully-functional airway which was rapidly vascularised, had normal mechanical properties and was free from the risk of rejection. These findings show how combining a donated decellularised scaffold with autologous cells can provide a successful treatment solution for patients with serious clinical disorders. It is hoped that the principals developed in this study can be extended to regenerate other organs in the future.

Keywords (Optional): 
Trachea Transplantation
Stem Cells
Tissue Engineering