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dc.contributor.authorJungebluth, Philipp
dc.contributor.authorAlici, Evren
dc.contributor.authorBaiguera, Silvia
dc.contributor.authorLe Blanc, Katarina
dc.contributor.authorBlomberg, Pontus
dc.contributor.authorBozóky, Béla
dc.contributor.authorCrowley, Claire
dc.contributor.authorEinarsson, Oskar
dc.contributor.authorGrinnemo, Karl-Henrik
dc.contributor.authorGudbjartsson, Tomas
dc.contributor.authorLe Guyader, Sylvie
dc.contributor.authorHenriksson, Gert
dc.contributor.authorHermanson, Ola
dc.contributor.authorJuto, Jan Erik
dc.contributor.authorLeidner, Bertil
dc.contributor.authorLilja, Tobias
dc.contributor.authorLiska, Jan
dc.contributor.authorLuedde, Tom
dc.contributor.authorLundin, Vanessa
dc.contributor.authorMoll, Guido
dc.contributor.authorNilsson, Bo
dc.contributor.authorRoderburg, Christoph
dc.contributor.authorStrömblad, Staffan
dc.contributor.authorSutlu, Tolga
dc.contributor.authorTeixeira, Ana Isabel
dc.contributor.authorWatz, Emma
dc.contributor.authorSeifalian, Alexander
dc.contributor.authorMacchiarini, Paolo
dc.date.accessioned2012-05-31T13:52:47Z
dc.date.available2012-05-31T13:52:47Z
dc.date.issued2011-12-10
dc.date.submitted2012-05-31
dc.identifier.citationLancet 2011, 378(9808):1997-2004en_GB
dc.identifier.issn1474-547X
dc.identifier.pmid22119609
dc.identifier.doi10.1016/S0140-6736(11)61715-7
dc.identifier.urihttp://hdl.handle.net/2336/226916
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractBACKGROUND: 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
dc.description.sponsorshipEuropean Commission 280584-2BIOtracheaCP-FPFP7-NMP-2011-SMALL-5 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) UCL Business Centre for Biosciences ERC-2007-Stg/208237-Luedde-Med3-Aachenen_GB
dc.language.isoenen
dc.publisherLancet Publishing Groupen_GB
dc.relation.urlhttp://dx.doi.org/10.1016/S0140-6736(11)61715-7en_GB
dc.rightsArchived with thanks to Lanceten_GB
dc.subject.meshAdulten_GB
dc.subject.meshBioreactorsen_GB
dc.subject.meshBlood Vessel Prosthesisen_GB
dc.subject.meshBone Marrow Transplantationen_GB
dc.subject.meshBronchial Neoplasmsen_GB
dc.subject.meshBronchoscopyen_GB
dc.subject.meshCarcinoma, Mucoepidermoiden_GB
dc.subject.meshCell Proliferationen_GB
dc.subject.meshErythropoietinen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshGranulocyte Colony-Stimulating Factoren_GB
dc.subject.meshHematopoietic Stem Cellsen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLeukocytes, Mononuclearen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMicroRNAsen_GB
dc.subject.meshNanocompositesen_GB
dc.subject.meshNeoplasm Recurrence, Localen_GB
dc.subject.meshNeovascularization, Physiologicen_GB
dc.subject.meshPolyethylene Terephthalatesen_GB
dc.subject.meshRecombinant Proteinsen_GB
dc.subject.meshRegenerationen_GB
dc.subject.meshTissue Engineeringen_GB
dc.subject.meshTissue Scaffoldsen_GB
dc.subject.meshTracheal Neoplasmsen_GB
dc.subject.meshTransplantation, Autologousen_GB
dc.titleTracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.en
dc.typeArticleen
dc.contributor.departmentAdvanced Center for Translational Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden.en_GB
dc.identifier.journalLanceten_GB
html.description.abstractBACKGROUND: 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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