In?Vivo Tissue Engineering of Human?Airways

摘要

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.;;The Supplemental MaterialsSupplemental Materials can be viewed in the online version of this article [http://dx.doi.org/10.1016/j.athoracsur.2016.11.027] on http://www.annalsthoracicsurgery.org.;Jump to SectionPatients and MethodsPatientsSurgical Procedure and Follow-upImmunohistochemical and XX/XY Chimerism StudiesCharacteristics of the Implanted CAA MatrixResultsClinical AspectsBiological AspectsCommentSupplementary DataReferences;The medical history, preoperative findings, and demographics?of the 2 patients are summarized in Table?1Table?1. A complex benign postintubation laryngotracheal stenosis associated with severe underlying general or local diseases, or both, had developed in both patients. They underwent multiple previous airway interventions for upper tracheal stenosis using conventional surgical and bronchoscopic management, which resulted in the extension of the stenoses to the subglottic larynx. Facing a therapeutic dead end, the placement of a permanent airway T-tube through a tracheostomy was performed (Supplemental Fig S1A–ESupplemental Fig S1A–E).Table?1Medical History, Preoperative and Perioperative Characteristics, and Follow-Up of the 2 PatientsCharacteristicPatient 1Patient 2GenderFemaleMaleAge, y5833Underlying general or local diseasesIdiopathic laryngeal edemaSevere epilepsy controlled by 4?drugsAirway intubation?CauseThyroidectomy for Basedow diseaseRefractory epileptic seizure?Duration4 hours1 week?Year19982009Airway stenosis siteLaryngotrachealLaryngotrachealPrevious SM?Number of attempts11?Month and yearJune 2010April 2009?Cause of failureUpper airway malaciaAnastomotic dehiscencePrevious EM?Attempts, No.13?Month and yearJune 2010April–Sept 2009?Cause of failureLaryngeal edemaStent migrationPreoperative pulmonary function tests?FEV1 (% predicted value)75NA?FIV1 (% predicted value)70NAPreoperative SGRQ?Total score (%)2,776.29 (70)193.04 (29)?Symptoms (%)410.26 (62)1,204.6 (100)?Activity (%)898.1 (74)1,584.63 (75)?Impact (%)1,467.93 (69)1,584.63 (75)Referred from another centerNoYesIntensive preoperative cardiorespiratory training,?wk33Date of operationOctober 2010October 2011Sex mismatch (D/R)YesYesLength of the graft, cm55Perioperative difficultiesNoNoPostoperative courseUneventfulUneventfulDays of hospitalization1410Removal of cannulaa21Local ev