RegenVOX. Stem-cell based, tissue engineered laryngeal replacement.

Irreversible damage to the larynx (?voice-box?) can result in considerable reduction in quality of life with problems breathing, speaking and swallowing, thus preventing the normal integration of people into society. The creation of a complete replacement would require complex muscular activity which is beyond the scope of the work we propose here. However, the successful restoration of critical structural support and a new lining would restore the joys of speech, swallowing and, indeed, normal human interaction to many people. We will build on the breakthrough we achieved by regenerating the trachea (?windpipe?) of a young woman in Spain by using patients? own stem cells and mucous membrane cells, combined with a non-rejecting matrix support, to restore parts of the larynx destroyed by disease, accident or cancer. This would be a major breakthrough for surgery and the lessons learnt will help the development of regenerative cures for a host of other diseases.

The overarching aim of this project is to optimise laryngeal cell and scaffold production prior to performing preclinical studies necessary for clinical trials, and demonstrate the feasibility of stem-cell based partial laryngeal regeneration in a pig model. Specific aim 1 is to develop Standard Operating Procedures to include Release Criteria and In-Process Quality Control for production of mesenchymal stem cell derived chondrocytes, airway epithelium and laryngeal scaffolds (synthetic and biologic). Specific aim 2 is to perform feasibility studies of partial laryngeal regeneration using human stem cells in pigs. Specific aim 3 is to maximise the economic and health benefits arising from the RegenVOX programme. This project forms part of an integrated programme of tissue regeneration at UCL. The long-term aim of this NHS- and UCL-backed programme is to deliver a new generation of hollow-organ therapies into clinical practice. We believe we possess a critical mass of multidisciplinary personnel and facilities (significantly reducing costs requested), the relevant commercialisation experience, and a high probability of outcome delivery within 2 years. We are unique in our ability to ability to deliver a first in man implants (as seen with our tracheal implant programme).