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Graupp, M; Rinner, B; Frisch, MT; Weiss, G; Fuchs, J; Sundl, M; El-Heliebi, A; Moser, G; Kamolz, LP; Karbiener, M; Gugatschka, M.
Towards an in vitro fibrogenesis model of human vocal fold scarring.
Eur Arch Otorhinolaryngol. 2018; 275(5):1211-1218
Doi: 10.1007/s00405-018-4922-7
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- Führende Autor*innen der Med Uni Graz
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Karbiener Michael
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Koiner-Graupp Matthias
- Co-Autor*innen der Med Uni Graz
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El-Heliebi Amin
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Fuchs Julia
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Gugatschka Markus
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Kamolz Lars-Peter
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Melcher Marie-Therese
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Moser Gerit
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Rinner Beate
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Sundl Monika
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Weiss Gregor
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- Abstract:
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Vocal fold (VF) scarring remains a therapeutic dilemma and challenge in modern laryngology. To facilitate corresponding research, we aimed to establish an in vitro fibrogenesis model employing human VF fibroblasts (hVFF) and the principles of macromolecular crowding (MMC).
Fibrogenesis was promoted by addition of transforming growth factor-β1 to standard medium and medium containing inert macromolecules (MMC). Hepatocyte growth factor (HGF) and Botox type A were tested for their antifibrotic properties in various doses. Experiments were analyzed with respect to the biosynthesis of collagen, fibronectin, and α-smooth muscle actin using immunofluorescence, silver stain and western blot.
MMC led to favourable enhanced deposition of collagen and other extracellular matrix components, reflecting fibrotic conditions. Low doses of HGF were able to dampen profibrotic effects. This could not be observed for higher HGF concentrations. Botox type A did not show any effects.
Based on the principles of MMC we could successfully establish a laryngeal fibrogenesis model employing hVFF. Our finding of dose-dependent HGF effects is important before going into clinical trials in humans and has never been shown before. Our model provides a novel option to screen various potential antifibrotic compounds under standardized conditions in a short time.
- Find related publications in this database (Keywords)
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Vocal fold fibroblasts
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Vocal fold scar
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In vitro fibrogenesis model
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Macromolecular crowding