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doi:10.22028/D291-36685
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Titel: | Murine Alveolar Epithelial Cells and Their Lentivirus-mediated Immortalisation |
VerfasserIn: | Sapich, Sandra Hittinger, Marius Hendrix-Jastrzebski, Remi Repnik, Urska Griffiths, Gareth May, Tobias Wirth, Dagmar Bals, Robert ![]() Schneider-Daum, Nicole Lehr, Claus-Michael ![]() |
Sprache: | Englisch |
In: | |
Titel: | Alternatives to Laboratory Animals |
Bandnummer: | 46 |
Heft: | 2 |
Seiten: | 73-89 |
Verlag/Plattform: | SAGE |
Erscheinungsjahr: | 2018 |
Freie Schlagwörter: | cytotoxicity mouse cell line pulmonary drug delivery respiratory in vitro model Three Rs |
DDC-Sachgruppe: | 500 Naturwissenschaften 610 Medizin, Gesundheit |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | In this study, we describe the isolation and immortalisation of primary murine alveolar epithelial cells (mAEpC), as well as their epithelial differentiation and barrier properties when grown on Transwell® inserts. Like human alveolar epithelial cells (hAEpC), mAEpC transdifferentiate in vitro from an alveolar type II (ATII) phenotype to an ATI-like phenotype and exhibit features of the air–blood barrier, such as the establishment of a thin monolayer with functional tight junctions (TJs). This is demonstrated by the expression of TJ proteins (ZO-1 and occludin) and the development of high transepithelial electrical resistance (TEER), peaking at 1800ω•cm2. Transport across the air–blood barrier, for general toxicity assessments or preclinical drug development, is typically studied in mice. The aim of this work was the generation of novel immortalised murine lung cell lines, to help meet Three Rs requirements in experimental testing and research. To achieve this goal, we lentivirally transduced mAEpC of two different mouse strains with a library of 33 proliferation-promoting genes. With this immortalisation approach, we obtained two murine alveolar epithelial lentivirus-immortalised (mAELVi) cell lines. Both showed similar TJ protein localisation, but exhibited less prominent barrier properties (TEERmax ~250Ω•cm2) when compared to their primary counterparts. While mAEpC demonstrated their suitability for use in the assessment of paracellular transport rates, mAELVi cells could potentially replace mice for the prediction of acute inhalation toxicity during early ADMET studies. |
DOI der Erstveröffentlichung: | 10.1177/026119291804600207 |
URL der Erstveröffentlichung: | https://journals.sagepub.com/doi/10.1177/026119291804600207 |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-366857 hdl:20.500.11880/33328 http://dx.doi.org/10.22028/D291-36685 |
ISSN: | 0261-1929 |
Datum des Eintrags: | 7-Jul-2022 |
Fakultät: | M - Medizinische Fakultät NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | M - Innere Medizin NT - Pharmazie |
Professur: | M - Prof. Dr. Robert Bals NT - Prof. Dr. Claus-Michael Lehr |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
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