title: An engineered 3D human airway mucosa model based on an SIS scaffold.
abstract: To investigate interrelations of human obligate airway pathogens, such as Bordetella pertussis, and their hosts test systems with high in vitro/in vivo correlation are of urgent need. Using a tissue engineering approach, we generated a 3D test system of the airway mucosa with human tracheobronchial epithelial cells (hTEC) and fibroblasts seeded on a clinically implemented biological scaffold. To investigate if hTEC display tumour-specific characteristics we analysed Raman spectra of hTEC and the adenocarcinoma cell line Calu-3. To establish optimal conditions for infection studies, we treated human native airway mucosa segments with B. pertussis. Samples were processed for morphologic analysis. Whereas our test system consisting of differentiated epithelial cells and migrating fibroblasts shows high in vitro/in vivo correlation, hTEC seeded on the scaffold as monocultures did not resemble the in vivo situation. Differences in Raman spectra of hTEC and Calu-3 were identified in distinct wave number ranges between 720 and 1662 cm(-1) indicating that hTEC do not display tumour-specific characteristics. Infection of native tissue with B. pertussis led to cytoplasmic vacuoles, damaged mitochondria and destroyed epithelial cells. Our test system is suitable for infection studies with human obligate airway pathogens by mimicking the physiological microenvironment of the human airway mucosa.
authors.affiliation: Fraunhofer Project Group Regenerative Technologies in Oncology, Röntgenring 11, 97070 Würzburg, Germany; University Hospital Würzburg, Tissue Engineering and Regenerative Medicine, Röntgenring 11, 97070 Würzburg, Germany. Electronic address: maria.steinke@igb.fraunhofer.de.
authors.forename: Maria
authors.initials: M
authors.lastname: Steinke
authors.affiliation: University of Würzburg, Department of Microbiology, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Roy
authors.initials: R
authors.lastname: Gross
authors.affiliation: Fraunhofer Project Group Regenerative Technologies in Oncology, Röntgenring 11, 97070 Würzburg, Germany; University Hospital Würzburg, Tissue Engineering and Regenerative Medicine, Röntgenring 11, 97070 Würzburg, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.affiliation: CellTool GmbH, Am Neuland 1, 82357 Bernried, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Gangnus
authors.affiliation: CellTool GmbH, Am Neuland 1, 82357 Bernried, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Schütze
authors.affiliation: University Hospital Würzburg, Department of Cardiothoracic Surgery, Oberdürrbacher Str. 6, 97080 Würzburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Walles
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry; D000818:Animals; D001886:Bordetella pertussis / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology / Q000473:pathology; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D020545:Respiratory Mucosa / Q000737:chemistry / Q000166:cytology* / Q000382:microbiology / Q000473:pathology; D013059:Spectrum Analysis, Raman; D013552:Swine; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*; D014917:Whooping Cough / Q000473:pathology
keywords: Airway epithelium; Immunohistochemistry; Raman micro spectroscopy; SIS; TEM