Controlled 3D culture in Matrigel microbeads to analyze clonal acinar development
Abstract
3D culture systems are a valuable tool for modeling morphogenesis and carcinogenesis of epithelial tissue in a structurally appropriate context. We present a novel approach for 3D cell culture based on a flow-focusing microfluidic system that encapsulates epithelial cells in Matrigel beads. As a model we use prostatic and breast cells and assay for development of acini, polarized cellular spheres enclosing lumen. Each individual bead on average acts as a single 3D cell culture compartment generating one acinus per bead. Compared to standard protocols microfluidics provides increased control over the environment leading to more a uniform acini population. The increased facility of bead manipulation allowed us to isolate single cells which are self-sufficient to fully develop into acini in presence of Matrigel. Furthermore, combination of our microfluidic approach with large particle FACS opens new avenues in high throughput screening on single acini or spheroids.
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The microfluidic setup allows automatic generation of homogeneous organoids embedded within microbeads of controlled size, composition and cell distribution.
“This setup allows the automatic generation of homogeneous organoids that are embedded within microbeads of controlled size, composition and cell distribution (Figure 1B–a) (20).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [20]
RWPE-1 cells are a model for normal prostate epithelial cell behavior, characterized by a polarized acinar morphology in 3D cultures.
“RWPE-1 cells were previously used as a model for normal prostate epithelial cell behavior, as characterized by a polarized acinar morphology in 3D cultures (20).”
From Direct transfection of clonal organoids in Matrigel microbeads: a promising approach toward organoid-based genetic screens (2018) · cites this paper as [20]
Cites
Micropatterning as a tool to decipher cell morphogenesis and functions
Théry, M. (2010) · Journal of Cell Science · doi:10.1242/jcs.075150 · Cited by 730 · see citing works
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Hofer, M., & Lutolf, M. P. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00279-y · Cited by 1,184 · see citing works
Laperrousaz, B., Porte, S., Gerbaud, S., Härmä, V., Kermarrec, F., Hourtane, V., Bottausci, F., Gidrol, X., & Picollet-D’hahan, N. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky030 · Cited by 54 · see citing works
“This setup allows the automatic generation of homogeneous organoids that are embedded within microbeads of controlled size, composition and cell distribution (Figure 1B-a) (20).”
MethodInfluentialSelf-citationYildiz-Ozturk, E., Gulce-Iz, S., Anil, M., & Yesil-Celiktas, O. (2017) · Cytotechnology · doi:10.1007/s10616-016-0062-3 · Cited by 32 · see citing works
Liu, J., Li, R., Xue, R., Li, T., Leng, L., Wang, Y., Wang, J., Ma, J., Yan, J., Yan, F., et al. (2018) · Advanced Biosystems · doi:10.1002/adbi.201800110 · Cited by 23 · see citing works
- Authors
- Dolega, M. E., Abeille, F., Picollet-D'hahan, N., & Gidrol, X.
- Affiliations
- Inserm (FR)
- Corresponding author
- Gidrol, Xavier
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-06
- Volume
- 52
- Pages
- 347-357
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2068790876
- Cited by
- 91
- References
- 1
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 5 · 2021: 10 · 2020: 8 · 2019: 4 · 2018: 17 · 2017: 8 · 2016: 8 · 2015: 3
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- CEA
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Physical Sciences › Engineering › Biomedical Engineering › Microfluidic and Capillary Electrophoresis Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- 3D cell culture, flow-focusing microfluidics, epithelial morphogenesis, prostate cells, breast cells, lumen formation, single-cell isolation, high-throughput screening, spheroids
- MeSH terms
- Breast Neoplasms, Cell Differentiation, Cell Separation, Cell Survival, Cells, Cultured, Collagen, Drug Combinations, Epithelial Cells, Female, Flow Cytometry, Humans, Laminin, Male, Prostatic Neoplasms, Proteoglycans, Tumor Cells, Cultured, Cell Culture Techniques, RNA, Small Interfering, Microfluidics, Acinar Cells
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