title: In Vivo Tissue Engineering of Human Airways.
abstract: BACKGROUND
  Airway transplantation remains a major challenge in thoracic surgery. Based on our previous laboratory work, we developed the techniques required to bioengineer a tracheal substitute in vivo using cryopreserved aortic allografts as biological matrices (Replacement of the Airways and/or the Pulmonary Vessels Using a Cryopreserved Arterial Allograft [TRACHEOBRONCART] Study, NCT01331863). We present here 2 patients who had a definitive tracheostomy for complex laryngotracheal stenoses refractory to conventional therapy.
  
  
  METHODS
  According to our protocol, a stented gender-mismatched -80°C cryopreserved aortic allograft was used for airway reconstruction. Follow-up assessments were done at regular intervals using clinical, imaging, and endoscopic evaluations. Immunohistochemical and XX/XY chimerism studies were performed at time of stent removal using graft biopsy specimens. Chemotactic and angiogenic properties of implanted matrices were also investigated.
  
  
  RESULTS
  At a maximal follow-up of 5 years and 7 months, the patients were breathing and speaking normally, without tracheostomy or stent. Regeneration of cartilage within the aortic grafts was demonstrated by positive immunodetection of type II collagen and markers specific for Sox9. Chimerism study from samples of neotissues demonstrated that regenerated cartilage came from recipient cells. The remaining viable matrix cells released a functionally relevant amount of proangiogenic, chemoattractant, proinflammatory/immunomodulatory cytokines, and growth factors.
  
  
  CONCLUSIONS
  This report documents the feasibility of in vivo tissue engineering for long-term functional airway transplantation in humans.
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Avicenne Hospital, Departments of Thoracic and Vascular Surgery, Pulmonology and Internal Medicine, Sorbonne Paris Cité, Paris 13 University, Faculty of Medicine SMBH, Bobigny, France; Sorbonne Paris Cité, Paris Descartes University, Alain Carpentier Foundation, Laboratory for Biosurgical Research, Assistance Publique-Hôpitaux de Paris, Georges Pompidou European Hospital, Paris, France. Electronic address: emmanuel.martinod@aphp.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Martinod
authors.affiliation: Sorbonne Paris Cité, Paris Diderot University, Laboratory of Bio-engineering and Osteo-Articular Biomaterial B20A, Paris, France.
authors.forename: Joseph
authors.initials: J
authors.lastname: Paquet
authors.affiliation: Assistance Publique-Hôpitaux de Marseille, Thoracic Oncology, Pleural Diseases and Interventional Pulmonology Department. North University Hospital, Marseille, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Dutau
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Avicenne Hospital, Departments of Thoracic and Vascular Surgery, Pulmonology and Internal Medicine, Sorbonne Paris Cité, Paris 13 University, Faculty of Medicine SMBH, Bobigny, France; Sorbonne Paris Cité, Paris Descartes University, Alain Carpentier Foundation, Laboratory for Biosurgical Research, Assistance Publique-Hôpitaux de Paris, Georges Pompidou European Hospital, Paris, France.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Radu
authors.affiliation: Sorbonne Paris Cité, Paris Diderot University, Laboratory of Bio-engineering and Osteo-Articular Biomaterial B20A, Paris, France.
authors.forename: Morad
authors.initials: M
authors.lastname: Bensidhoum
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Avicenne Hospital, Departments of Thoracic and Vascular Surgery, Pulmonology and Internal Medicine, Sorbonne Paris Cité, Paris 13 University, Faculty of Medicine SMBH, Bobigny, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Abad
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Seine-Saint-Denis, Avicenne Hospital, Departments of Thoracic and Vascular Surgery, Pulmonology and Internal Medicine, Sorbonne Paris Cité, Paris 13 University, Faculty of Medicine SMBH, Bobigny, France.
authors.forename: Yurdagül
authors.initials: Y
authors.lastname: Uzunhan
authors.affiliation: Assistance Publique-Hôpitaux de Paris, Clinical Research Unit, Fernand Widal Hospital, Sorbonne Paris Cité, Paris Diderot University, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: Sorbonne Paris Cité, Paris Diderot University, Laboratory of Bio-engineering and Osteo-Articular Biomaterial B20A, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Petite
mesh_terms: D000328:Adult; D001011:Aorta / Q000637:transplantation*; D015925:Cryopreservation; D005260:Female; D006801:Humans; D007818:Laryngeal Diseases / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015607:Stents; D023822:Tissue Engineering / Q000379:methods*; D014132:Trachea / Q000166:cytology / Q000502:physiology* / Q000601:surgery; D014135:Tracheal Stenosis / Q000601:surgery*; D014184:Transplantation, Homologous