In Vivo Tissue Engineering of Human Airways

Abstract

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 invivo 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. 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. 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. This report documents the feasibility of invivo tissue engineering for long-term functional airway transplantation in humans.