title: Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study.
abstract: In 2010, a tissue-engineered trachea was transplanted into a 10-year-old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti-HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross-sectional area analysis showed restriction of growth within an area of in-stent stenosis. This report demonstrates the long-term viability of a decellularized tissue-engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.
authors.affiliation: University College London Ear Institute, Royal National Throat Nose and Ear Hospital, London, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Hamilton
authors.affiliation: Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Kanani
authors.affiliation: Department of Radiology, Great Ormond Street Hospital, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Roebuck
authors.affiliation: Department of Otorhinolaryngology, Great Ormond Street Hospital, London, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hewitt
authors.affiliation: Imperial College London, Department of Aeronautics, London, UK.
authors.forename: R
authors.initials: R
authors.lastname: Cetto
authors.affiliation: London Regenerative Medicine Network, London, UK.
authors.forename: E J
authors.initials: EJ
authors.lastname: Culme-Seymour
authors.affiliation: Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London, UK.
authors.forename: E
authors.initials: E
authors.lastname: Toll
authors.affiliation: Imperial College London, Department of Aeronautics, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Bates
authors.affiliation: Imperial College London, Department of Aeronautics, London, UK.
authors.forename: A P
authors.initials: AP
authors.lastname: Comerford
authors.affiliation: Department of Radiology, Great Ormond Street Hospital, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: McLaren
authors.affiliation: Lungs for Living Research Centre, Rayne Institute, London, UK.
authors.forename: C R
authors.initials: CR
authors.lastname: Butler
authors.affiliation: University College London Centre for Nanotechnology and Regenerative Medicine, Royal Free Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Crowley
authors.affiliation: Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: McIntyre
authors.affiliation: Department of Histopathology, Great Ormond Street Hospital, London, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Sebire
authors.affiliation: Lungs for Living Research Centre, Rayne Institute, London, UK.
authors.forename: S M
authors.initials: SM
authors.lastname: Janes
authors.affiliation: Department of Respiratory Medicine, Great Ormond Street Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: London Regenerative Medicine Network, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Mason
authors.affiliation: Department of Surgery, Great Ormond Street Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: De Coppi
authors.affiliation: Department of Haematology, Royal Free Hospital, University College London Paul O'Gorman Laboratory of Cellular Therapeutics, London, UK.
authors.forename: M W
authors.initials: MW
authors.lastname: Lowdell
authors.affiliation: Department of Cardiothoracic Surgery, Great Ormond Street Hospital, London, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Elliott
authors.affiliation: University College London Ear Institute, Royal National Throat Nose and Ear Hospital, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Birchall
mesh_terms: D002648:Child; D006801:Humans; D023822:Tissue Engineering / Q000379:methods*; D014132:Trachea / Q000637:transplantation*
keywords: Graft survival; growth and development; tissue/organ engineering