Scalable fabrication of renal spheroids and nephron-like tubules by bioprinting and controlled self-assembly of epithelial cells
| Autor: | Kevin Troendle, Stefan Zimmermann, Fritz Koch, Roman Pichler, Peter Koltay, Roland Zengerle, Ahmad Itani, Ludovica Rizzo, Soeren S. Lienkamp |
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| Přispěvatelé: | University of Zurich |
| Rok vydání: | 2021 |
| Předmět: |
Cell type
Fabrication 10017 Institute of Anatomy 0206 medical engineering Hydrostatic pressure Biomedical Engineering Bioengineering 610 Medicine & health Cell Count 02 engineering and technology Nephron Kidney Biochemistry Biomaterials Mice Spheroids Cellular medicine Animals Humans Tight junction Spheroid Bioprinting Epithelial Cells General Medicine Nephrons 021001 nanoscience & nanotechnology 020601 biomedical engineering medicine.anatomical_structure MRNA Sequencing 10076 Center for Integrative Human Physiology 570 Life sciences biology 0210 nano-technology Biotechnology Biomedical engineering Lumen (unit) |
| Zdroj: | Biofabrication |
| ISSN: | 1758-5082 |
| DOI: | 10.1088/1758-5090/abe185 |
| Popis: | Scalable fabrication concepts of 3D kidney tissue models are required to enable their application in pharmaceutical high-throughput screenings. Yet the reconstruction of complex tissue structures remains technologically challenging. We present a novel concept reducing the fabrication demands, by using controlled cellular self-assembly to achieve higher tissue complexities from significantly simplified construct designs. We used drop-on-demand bioprinting to fabricate locally confined patterns of renal epithelial cells embedded in a hydrogel matrix. These patterns provide defined local cell densities (cell count variance µm in diameter (size variance µm). These showed a continuous lumen with prescribed orientation, lined by an epithelial monolayer with tight junctions. Additionally, upregulated expression of kidney-specific functional genes compared to 2D cell monolayers indicated increased tissue functionality, as revealed by mRNA sequencing. Furthermore, our concept enabled the fabrication of hybrid tubules, which consisted of arranged subsections of different cell types, combining murine and human epithelial cells. Finally, we integrated the self-assembled fabrication into a microfluidic chip and achieved fluidic access to the lumen at the terminal sites of the tubules. With this, we realized flow conditions with a wall shear stress of 0.05 ± 0.02 dyne cm−2 driven by hydrostatic pressure for scalable dynamic culture towards a nephron-on-chip model. |
| Databáze: | OpenAIRE |
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