The first tissue-engineered airway transplantation: 5-year follow-up results

BACKGROUND In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. We report 5 year follow-up results. METHODS The patient was followed up approximately every 3 months with multidetector CT scan and bronchoscopic assessment. We obtained mucosal biopsy samples every 6 months for histological, immunohistochemical, and electron microscopy assessment. We also assessed quality of life, respiratory function, cough reflex test, and production and specificity of recipient antibodies against donor human leucocyte antigen. FINDINGS By 12 months after transplantation, a progressive cicatricial stenosis had developed in the native trachea close to the tissue-engineered trachea anastomosis, which needed repeated endoluminal stenting. However, the tissue-engineered trachea itself remained open over its entire length, well vascularised, completely re-cellularised with respiratory epithelium, and had normal ciliary function and mucus clearance. Lung function and cough reflex were normal. No stem-cell-related teratoma formed and no anti-donor antibodies developed. Aside from intermittent bronchoscopic interventions, the patient had a normal social and working life. INTERPRETATION These clinical results provide evidence that a tissue-engineering strategy including decellularisation of a human trachea, autologous epithelial and stem-cell culture and differentiation, and cell-scaffold seeding with a bioreactor is safe and promising. FUNDING European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, ALF Medicine.

[1]  Biju Parekkadan,et al.  Mesenchymal stem cells as therapeutics. , 2010, Annual review of biomedical engineering.

[2]  A. Webster,et al.  Consensus Guidelines on the Testing and Clinical Management Issues Associated With HLA and Non-HLA Antibodies in Transplantation , 2013, Transplantation.

[3]  M. Elliott,et al.  First experience with biodegradable airway stents in children. , 2011, The Annals of thoracic surgery.

[4]  J. Zwischenberger,et al.  Tracheal Replacements: Part 1 , 2007, ASAIO journal.

[5]  H. Mertsching,et al.  First human transplantation of a bioengineered airway tissue. , 2004, The Journal of thoracic and cardiovascular surgery.

[6]  E. Snyder,et al.  A safer stem cell: on guard against cancer , 2009, Nature Medicine.

[7]  R. Deitch.  Commentary from Westminster. Abortion (Amendment) Bill. , 1980, Lancet.

[8]  Korkut Uygun,et al.  Whole-organ tissue engineering: decellularization and recellularization of three-dimensional matrix scaffolds. , 2011, Annual review of biomedical engineering.

[9]  Robert L Sah,et al.  The impact of biomechanics in tissue engineering and regenerative medicine. , 2009, Tissue engineering. Part B, Reviews.

[10]  P. Terasaki,et al.  Predicting Kidney Graft Failure by HLA Antibodies: a Prospective Trial , 2004, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[11]  Paolo De Coppi,et al.  Tissue engineered human tracheas for in vivo implantation. , 2010, Biomaterials.

[12]  K. Sesterhenn,et al.  TRACHEAL ALLOTRANSPLANTATION IN MAN , 1979, The Lancet.

[13]  James J. Yoo,et al.  Tissue-engineered autologous bladders for patients needing cystoplasty , 2006, The Lancet.

[14]  J. Wallwork,et al.  Airway complications after lung transplantation: is there a left-sided predilection? , 1995, The Journal of thoracic and cardiovascular surgery.

[15]  C. Tarsitani,et al.  Simultaneous HLA Class I and Class II antibodies screening with flow cytometry. , 1998, Human immunology.

[16]  J. Zwischenberger,et al.  Tracheal Replacements: Part 2 , 2007, ASAIO journal.

[17]  Lutz Freitag,et al.  A proposed classification system of central airway stenosis , 2007, European Respiratory Journal.

[18]  G. Verleden,et al.  Tracheal allotransplantation after withdrawal of immunosuppressive therapy. , 2010, The New England journal of medicine.

[19]  J. G. Weg,et al.  Diagnosis of upper airway obstruction by pulmonary function testing. , 1975, Chest.

[20]  T. Walles,et al.  Clinical tracheal replacement: transplantation, bioprostheses and artificial grafts , 2008, Expert review of medical devices.

[21]  A. Atala,et al.  Scaffold technologies for controlling cell behavior in tissue engineering. , 2013, Biomedical materials.

[22]  R. Cotton,et al.  Historical Development of Surgery for Pediatric Laryngeal Stenosis , 1995, Ear, nose, & throat journal.

[23]  Stephen F Badylak,et al.  Prevention of seroma formation with TissuGlu® surgical adhesive in a canine abdominoplasty model: long term clinical and histologic studies. , 2013, Journal of plastic, reconstructive & aesthetic surgery : JPRAS.

[24]  F. Lavorini,et al.  A noninvasive electromyographic study on threshold and intensity of cough in humans. , 1997, The European respiratory journal.

[25]  T. Pruett.  Tracheal Allotransplantation after Withdrawal of Immunosuppressive Therapy , 2011 .

[26]  F. Benvenuti,et al.  Defective motor control of coughing in Parkinson's disease. , 1998, American journal of respiratory and critical care medicine.

[27]  Hermes C Grillo,et al.  Tracheal replacement: a critical review. , 2002, The Annals of thoracic surgery.

[28]  Doris A Taylor,et al.  Long-term changes to in vitro preserved bioengineered human trachea and their implications for decellularized tissues. , 2012, Biomaterials.

[29]  Yimin Zhao,et al.  Clinical transplantation of a tissue-engineered airway , 2009, The Lancet.

[30]  J. Widdicombe,et al.  Fog-induced cough with impaired respiratory sensation in congenital central hypoventilation syndrome. , 2007, American journal of respiratory and critical care medicine.