title: Stem-cell-based, tissue engineered tracheal replacement in a child: a 2-year follow-up study.
abstract: BACKGROUND
  Stem-cell-based, tissue engineered transplants might offer new therapeutic options for patients, including children, with failing organs. The reported replacement of an adult airway using stem cells on a biological scaffold with good results at 6 months supports this view. We describe the case of a child who received a stem-cell-based tracheal replacement and report findings after 2 years of follow-up.
  
  
  METHODS
  A 12-year-old boy was born with long-segment congenital tracheal stenosis and pulmonary sling. His airway had been maintained by metal stents, but, after failure, a cadaveric donor tracheal scaffold was decellularised. After a short course of granulocyte colony stimulating factor, bone marrow mesenchymal stem cells were retrieved preoperatively and seeded onto the scaffold, with patches of autologous epithelium. Topical human recombinant erythropoietin was applied to encourage angiogenesis, and transforming growth factor β to support chondrogenesis. Intravenous human recombinant erythropoietin was continued postoperatively. Outcomes were survival, morbidity, endoscopic appearance, cytology and proteomics of brushings, and peripheral blood counts.
  
  
  RESULTS
  The graft revascularised within 1 week after surgery. A strong neutrophil response was noted locally for the first 8 weeks after surgery, which generated luminal DNA neutrophil extracellular traps. Cytological evidence of restoration of the epithelium was not evident until 1 year. The graft did not have biomechanical strength focally until 18 months, but the patient has not needed any medical intervention since then. 18 months after surgery, he had a normal chest CT scan and ventilation-perfusion scan and had grown 11 cm in height since the operation. At 2 years follow-up, he had a functional airway and had returned to school.
  
  
  CONCLUSIONS
  Follow-up of the first paediatric, stem-cell-based, tissue-engineered transplant shows potential for this technology but also highlights the need for further research.
  
  
  BACKGROUND
  Great Ormond Street Hospital NHS Trust, The Royal Free Hampstead NHS Trust, University College Hospital NHS Foundation Trust, and Region of Tuscany.
authors: Department of Cardiothoracic Surgery, Great Ormond Street, Hospital for Children, London, UK.
authors: Martin J
authors: MJ
authors: Elliott
authors: Paolo
authors: P
authors: De Coppi
authors: Simone
authors: S
authors: Speggiorin
authors: Derek
authors: D
authors: Roebuck
authors: Colin R
authors: CR
authors: Butler
authors: Edward
authors: E
authors: Samuel
authors: Claire
authors: C
authors: Crowley
authors: Clare
authors: C
authors: McLaren
authors: Anja
authors: A
authors: Fierens
authors: David
authors: D
authors: Vondrys
authors: Lesley
authors: L
authors: Cochrane
authors: Christopher
authors: C
authors: Jephson
authors: Samuel
authors: S
authors: Janes
authors: Nicholas J
authors: NJ
authors: Beaumont
authors: Tristan
authors: T
authors: Cogan
authors: Augustinus
authors: A
authors: Bader
authors: Alexander M
authors: AM
authors: Seifalian
authors: J Justin
authors: JJ
authors: Hsuan
authors: Mark W
authors: MW
authors: Lowdell
authors: Martin A
authors: MA
authors: Birchall
mesh_terms: D002648:Child; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D014132:Trachea / Q000637:transplantation*; D014135:Tracheal Stenosis / Q000151:congenital / Q000473:pathology / Q000601:surgery*
chemical_list: D016179:Granulocyte Colony-Stimulating Factor