Tissue-Engineered Tracheal Replacement in a Child: A 4-Year Follow-Up Study

Abstract

In 2010, a tissue‐engineered trachea was transplanted into a 10‐year‐old child using a decellularized deceased donor trachea repopulated with the recipient's respiratory epithelium and mesenchymal stromal cells. We report the child's clinical progress, tracheal epithelialization and costs over the 4 years. A chronology of events was derived from clinical notes and costs determined using reference costs per procedure. Serial tracheoscopy images, lung function tests and anti‐HLA blood samples were compared. Epithelial morphology and T cell, Ki67 and cleaved caspase 3 activity were examined. Computational fluid dynamic simulations determined flow, velocity and airway pressure drops. After the first year following transplantation, the number of interventions fell and the child is currently clinically well and continues in education. Endoscopy demonstrated a complete mucosal lining at 15 months, despite retention of a stent. Histocytology indicates a differentiated respiratory layer and no abnormal immune activity. Computational fluid dynamic analysis demonstrated increased velocity and pressure drops around a distal tracheal narrowing. Cross‐sectional area analysis showed restriction of growth within an area of in‐stent stenosis. This report demonstrates the long‐term viability of a decellularized tissue‐engineered trachea within a child. Further research is needed to develop bioengineered pediatric tracheal replacements with lower morbidity, better biomechanics and lower costs.

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering

“…of some interventions, and an inability to study cell fate in humans means that little is known about their contribution. Clinical observations showed that patients were slow to regenerate healthy mucosa (3,4,15,16). High cell-seeding densities are required for bioengineering applications and, given the large surface area of clinical tracheal grafts, obtaining sufficient numbers of autologous epithelial cells is a challenge for the field.…”

A reassessment of tracheal substitutes—a systematic review

“…Aside from the work performed by the Macchiarini group, two pediatric patients have undergone treatment with tissue engineered tracheal conduits (26,28,29). Both patients suffered from severe congenital airway defects and had undergone multiple prior corrective procedures.…”

Airway tissue engineering for congenital laryngotracheal disease

“…Notwithstanding these issues, tracheal tissue engineering raises fewer potential ethical objections as an experimental therapy than in other clinical niches, given the total lack of alternative treatment options, and the greater intrinsic regenerative potential of pediatric patients compared to adults increases the likelihood of success. As such, regenerative approaches in the trachea have outstripped other organs in terms of high profile clinical compassionate cases both in adults [23], and in children [24,25].…”