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Regeneration of a well-differentiated human airway surface epithelium by spheroid and lentivirus vector-transduced airway cells.

Castillon, N; Avril-Delplanque, A; Coraux, C; Delenda, C; Péault, B; Danos, O; Puchelle, E; (2004) Regeneration of a well-differentiated human airway surface epithelium by spheroid and lentivirus vector-transduced airway cells. J Gene Med , 6 (8) pp. 846-856. 10.1002/jgm.570.

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Abstract

BACKGROUND: Following injury to the airway epithelium, rapid regeneration of a functional epithelium is necessary in order to restore the epithelial barrier integrity. In the perspective of airway gene/cell therapy, we analyzed the capacity of human airway epithelial cells cultured as three-dimensional (3-D) spheroid structures to be efficiently transduced on long term by a pseudotyped lentiviral vector. The capacity of the 3-D spheroid structures to repopulate a denuded tracheal basement membrane and regenerate a well-differentiated airway epithelium was also analyzed. METHODS: An HIV-1-derived VSV-G pseudotyped lentiviral vector encoding the enhanced green fluorescent protein (eGFP) was used. Airway epithelial cells were isolated from mature human fetal tracheas and airway xenografts, cultured as 3-D spheroid structures, and either transduced at multiplicity of infection (MOI) 10 and 100 or assayed in an ex vivo and in vivo model to evaluate their regeneration capacity. RESULTS: An in vivo repopulation assay in SCID-hu mice with transduced isolated fetal airway epithelial cells shows that lentiviral transduction does not alter the airway reconstitution. Transduction of the 3-D spheroid structures shows that 12% of cells were eGFP-positive for up to 80 days. In ex vivo and in vivo assays (NUDE-hu mice), the 3-D spheroid structures are able to repopulate denuded basement membrane and reconstitute a well-differentiated human airway surface epithelium. CONCLUSIONS: The efficient and long-term lentiviral transduction of 3-D spheroid structures together with their capacity to regenerate a well-differentiated mucociliary epithelium demonstrate the potential relevance of these 3-D structures in human airway gene/cell therapy.

Type: Article
Title: Regeneration of a well-differentiated human airway surface epithelium by spheroid and lentivirus vector-transduced airway cells.
Location: England
DOI: 10.1002/jgm.570
Keywords: Animals, Cell Differentiation, Cells, Cultured, Epithelial Cells, Epithelium, Gene Transfer Techniques, Genetic Vectors, Humans, Lentivirus, Mice, Mice, Nude, Microscopy, Fluorescence, Regeneration, Spheroids, Cellular, Trachea, Transduction, Genetic
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/90979
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