Biophysical Control of Bile Duct Epithelial Morphogenesis in Natural and Synthetic Scaffolds - Institut Pasteur Accéder directement au contenu
Article Dans Une Revue Frontiers in Bioengineering and Biotechnology Année : 2019

Biophysical Control of Bile Duct Epithelial Morphogenesis in Natural and Synthetic Scaffolds

Résumé

The integration of bile duct epithelial cells (cholangiocytes) in artificial liver culture systems is important in order to generate more physiologically relevant liver models. Understanding the role of the cellular microenvironment on differentiation, physiology, and organogenesis of cholangiocytes into functional biliary tubes is essential for the development of new liver therapies, notably in the field of cholangiophaties. In this study, we investigated the role of natural or synthetic scaffolds on cholangiocytes cyst growth, lumen formation and polarization. We demonstrated that cholangiocyte cyst formation efficiency can be similar between natural and synthetic matrices provided that the mechanical properties of the hydrogels are matched. When using synthetic matrices, we also tried to understand the impact of elasticity, matrix metalloprotease-mediated degradation and integrin ligand density on cyst morphogenesis. We demonstrated that hydrogel stiffness regulates cyst formation. We found that controlling integrin ligand density was key in the establishment of large polarized cysts of cholangiocytes. The mechanism of lumen formation was found to rely on cell self-organization and proliferation. The formed cholangiocyte organoids showed a good MDR1 (multi drug resistance protein) transport activity. Our study highlights the advantages of fully synthetic scaffold as a tool to develop bile duct models.
Fichier principal
Vignette du fichier
fbioe-07-00417.pdf (1.1 Mo) Télécharger le fichier
Loading...

Dates et versions

pasteur-02936645 , version 1 (11-09-2020)

Licence

Paternité

Identifiants

Citer

Anette Funfak, Latifa Bouzhir, Emilie Gontran, Nicolas Minier, Pascale Dupuis-Williams, et al.. Biophysical Control of Bile Duct Epithelial Morphogenesis in Natural and Synthetic Scaffolds. Frontiers in Bioengineering and Biotechnology, 2019, 7, pp.417. ⟨10.3389/fbioe.2019.00417⟩. ⟨pasteur-02936645⟩
108 Consultations
169 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More