Hong Kong Respiratory Medicine

Philipp Jungebluth, Evren Alici, Silvia Baiguera , Katarina Le Blanc , Pontus Blomberg , Béla Bozóky , Claire Crowley , Oskar Einarsson , Karl-Henrik Grinnemo l, Tomas Gudbjartsson , Sylvie Le Guyader, Gert Henriksson , Ola Hermanson, Jan Erik Juto , Bertil Leidner , Tobias Lilja, Jan Liska , Tom Luedde , Vanessa Lundin, Guido Moll , Prof Bo Nilsson , Christoph Roderburg,  Prof Staffan Strömblad , Tolga Sutlu , Ana Isabel Teixeira , Emma Watz MD,  Alexander Seifalian ,Paolo Macchiarini.  The Lancet, Volume 378, Issue 9808, Pages 1997 - 2004, 10 December 2011doi:10.1016/S0140-6736(11) 61715-7


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.

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