4.6 Article

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

期刊

AMERICAN JOURNAL OF TRANSPLANTATION
卷 15, 期 10, 页码 2750-2757

出版社

WILEY-BLACKWELL
DOI: 10.1111/ajt.13318

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资金

  1. Great Ormond Street Hospital NHS Trust (London, England)
  2. Royal Free Hampstead NHS Trust (London, England)
  3. University College Hospital NHS Foundation Trust (London, England)
  4. Region of Tuscany (Italy) [pd 239- 28/04/2009, delib. GRT 1210/08]
  5. UK Department of Health's National Institute for Health Research Biomedical Research Centres scheme
  6. National Health Service National Commissioning Mechanisms
  7. Wellcome Trust
  8. Medical Research Council Translational Stem Cell Research Committee grant [G1001539]
  9. Great Ormond Street Hospital Charity grant
  10. Engineering and Physical Sciences Research Council [1117520] Funding Source: researchfish
  11. Medical Research Council [G1001539, MR/L002000/1, MR/K026453/1] Funding Source: researchfish
  12. National Institute for Health Research [RP_2014-04-046, NF-SI-0513-10089] Funding Source: researchfish
  13. MRC [G1001539, MR/K026453/1, MR/L002000/1] Funding Source: UKRI

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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.

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