title: Stem Cell-Based Tissue-Engineered Laryngeal Replacement.
abstract: 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.
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom.
authors.forename: Tahera
authors.initials: T
authors.lastname: Ansari
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom.|University College London Ear Institute, Royal National Throat Nose and Ear Hospital, London, United Kingdom.
authors.forename: Peggy
authors.initials: P
authors.lastname: Lange
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom.
authors.forename: Aaron
authors.initials: A
authors.lastname: Southgate
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom.
authors.forename: Karin
authors.initials: K
authors.lastname: Greco
authors.affiliation: Department of Haematology, University College London Medical School, London, United Kingdom.
authors.forename: Carla
authors.initials: C
authors.lastname: Carvalho
authors.affiliation: Department of Haematology, University College London Medical School, London, United Kingdom.
authors.forename: Leanne
authors.initials: L
authors.lastname: Partington
authors.affiliation: Department of Material Science and Engineering, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bullock
authors.affiliation: Department of Material Science and Engineering, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Sheila
authors.initials: S
authors.lastname: MacNeil
authors.affiliation: Department of Haematology, University College London Medical School, London, United Kingdom.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Lowdell
authors.affiliation: Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Sibbons
authors.affiliation: University College London Ear Institute, Royal National Throat Nose and Ear Hospital, London, United Kingdom.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Birchall
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001999:Bronchoscopy; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007830:Larynx / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010699:Phonation; D020127:Recovery of Function; D012038:Regeneration; D034421:Sus scrofa; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014057:Tomography, X-Ray Computed; D014828:Vocalization, Animal
keywords: Animal model; Human stem cell; Larynx; Tissue engineering; Tissue scaffold