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.