- 作者：Aless ; ro Gonfiotti ; Massimo O Jaus ; Daniel Barale ; Silvia Baiguera ; Camilla Comin ; Federico Lavorini ; Giovanni Fontana ; Oriol Sibila ; Giovanni Rombol脿 ; Philipp Jungebluth ; Paolo Macchiarini
- 刊名：The Lancet
- 出版年：18-24 January, 2014
- 年：2014
- 卷：383
- 期：9913
- 页码：238-244
- 全文大小：2592 K
Summary
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.