Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study

Lancet. 2011 Dec 10;378(9808):1997-2004. doi: 10.1016/S0140-6736(11)61715-7. Epub 2011 Nov 24.


Background: Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite.

Methods: A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 μg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses.

Findings: We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft.

Interpretation: Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome.

Funding: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adult
  • Bioreactors
  • Blood Vessel Prosthesis
  • Bone Marrow Transplantation
  • Bronchial Neoplasms / surgery*
  • Bronchoscopy
  • Carcinoma, Mucoepidermoid / surgery
  • Cell Proliferation
  • Epoetin Alfa
  • Erythropoietin / therapeutic use
  • Flow Cytometry
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / transplantation*
  • Male
  • MicroRNAs / metabolism
  • Nanocomposites / chemistry
  • Neoplasm Recurrence, Local / surgery
  • Neovascularization, Physiologic
  • Polyethylene Terephthalates
  • Recombinant Proteins / therapeutic use
  • Regeneration
  • Tissue Engineering / methods*
  • Tissue Scaffolds*
  • Tracheal Neoplasms / surgery*
  • Transplantation, Autologous


  • MIRN16 microRNA, human
  • MIRN34 microRNA, human
  • MIRN449 microRNA, human
  • MicroRNAs
  • Polyethylene Terephthalates
  • Recombinant Proteins
  • Erythropoietin
  • Granulocyte Colony-Stimulating Factor
  • Epoetin Alfa