Stem Cell‐Based Tissue‐Engineered Laryngeal Replacement

• Published in: Stem cells translational medicine Vol. 6; no. 2; pp. 677 - 687
• Main Authors: Ansari, Tahera, Lange, Peggy, Southgate, Aaron, Greco, Karin, Carvalho, Carla, Partington, Leanne, Bullock, Anthony, MacNeil, Sheila, Lowdell, Mark W., Sibbons, Paul D., Birchall, Martin A.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-02-2017; John Wiley and Sons Inc
• Subjects: Animal model; Animals; Biomechanical Phenomena; Bone marrow; Bronchoscopy; Cartilage; Cell Proliferation; Cells, Cultured; Clinical trials; Collagen; Computed tomography; Detergents; Epithelium; Female; Fibroblasts; Human stem cell; Humans; Laboratories; Laryngeal cancer; Larynx; Larynx - diagnostic imaging; Larynx - pathology; Larynx - physiopathology; Larynx - transplantation; Medical research; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - physiology; Mesenchyme; Morbidity; Mucosa; Ostomy; Phonation; Recovery of Function; Regeneration; Respiratory function; Stem cell transplantation; Stem cells; Sus scrofa; Swallowing; Time Factors; Tissue engineering; Tissue Engineering - methods; Tissue Engineering and Regenerative Medicine; Tissue scaffold; Tissue Scaffolds; Tomography, X-Ray Computed; Translational s and Reviews; Transplants & implants; Trauma; Vocal organs; Vocalization, Animal; United Kingdom > UK; Animal model; Tissue scaffold; Human stem cell; Larynx; Tissue engineering
• ISSN: 2157-6564; 2157-6580
• DOI: 10.5966/sctm.2016-0130

Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue‐engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the regenerated tissue. Under Good Laboratory Practice conditions, we decellularized porcine larynges, using detergents and enzymes under negative pressure to produce an acellular scaffold comprising cartilage, muscle, and mucosa. To assess safety and functionality before clinical trials, a decellularized hemilarynx seeded with human bone marrow‐derived mesenchymal stem cells and a tissue‐engineered oral mucosal sheet was implanted orthotopically into six pigs. The seeded grafts were left in situ for 6 months and assessed using computed tomography imaging, bronchoscopy, and mucosal brushings, together with vocal recording and histological analysis on explantation. The graft caused no adverse respiratory function, nor did it impact swallowing or vocalization. Rudimentary vocal folds covered by contiguous epithelium were easily identifiable. In conclusion, the proposed tissue‐engineered approach represents a viable alternative treatment for laryngeal defects. Stem Cells Translational Medicine 2017;6:677–687