Micropattern-based platform as a physiologically relevant model to study epithelial morphogenesis and nephrotoxicity
| Autor: | Maria D. Barea, Gonzalo Herranz, Benoit Ladoux, Fernando Martín-Belmonte, Joanne Young, Minerva Bosch-Fortea, Mariam Hachimi, Alejo E. Rodriguez-Fraticelli |
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| Přispěvatelé: | Cell Biology and Biophysics Programme, EMBL, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
Biophysics
Morphogenesis Fluorescent Antibody Technique Bioengineering 02 engineering and technology Cell Line Biomaterials Extracellular matrix [SPI]Engineering Sciences [physics] 03 medical and health sciences Dogs In vivo Extracellular Cell Adhesion Animals ComputingMilieux_MISCELLANEOUS 030304 developmental biology Cell Proliferation Tube formation 0303 health sciences Microscopy Confocal Drug discovery Chemistry Cell Polarity 021001 nanoscience & nanotechnology Cell biology Tubule Kidney Tubules Drug development Mechanics of Materials Ceramics and Composites 0210 nano-technology Cell Division |
| Zdroj: | Biomaterials Biomaterials, Elsevier, 2019, 218, pp.119339. ⟨10.1016/j.biomaterials.2019.119339⟩ |
| ISSN: | 1878-5905 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2019.119339⟩ |
| Popis: | Tubulogenesis in epithelial organs often initiates with the acquisition of apicobasal polarity, giving rise to the formation of small lumens that expand and fuse to generate a single opened cavity. In this study, we present a micropattern-based device engineered to generate epithelial tubes through a process that recapitulates in vivo tubule morphogenesis. Interestingly, tubulogenesis in this device is dependent on microenvironmental cues such as cell confinement, extracellular matrix composition, and substrate stiffness, and our set-up specifically allows the control of these extracellular conditions. Additionally, proximal tubule cell lines growing on micropatterns express higher levels of drug transporters and are more sensitive to nephrotoxicity. These tubes display specific morphological defects that can be linked to nephrotoxicity, which would be helpful to predict potential toxicity when developing new compounds. This device, with the ability to recapitulate tube formation in vitro, has emerged as a powerful tool to study the molecular mechanisms involved in organogenesis and, by being more physiologically relevant than existing cellular models, becomes an innovative platform to conduct drug discovery assays. |
| Databáze: | OpenAIRE |
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