An artificial three-dimensional matrix promotes ramification in the microglial cell-line, BV-2
Abstract
Three-dimensional (3D) cell culture yields strikingly different cell phenotypes compared to two-dimensional (2D) cell culture. Since microglia, monocyte derived immune cells in the brain, exist in a variety of cell shapes ranging from amoeboid to ramified, we evaluated the impact of 2D versus 3D culture conditions on cell shape. The microglial cell-line, BV-2, was either cultured on poly-D-lysine coated dishes (2D culture conditions) or in a BD Pura Matrix Peptide Hydrogel (3D culture conditions) in the absence or presence of the extracellular matrix proteins, fibronectin and collagen type I, respectively. We identified five distinct morphological phenotypes (amoeboid, bipolar, tripolar, multipolar, ramified) and compared the frequency distribution of these phenotypes under different culture conditions using a chi(2) test. Culture of BV-2 cells in an inert 3D matrix shifted the frequency distribution from an amoeboid dominated population, which is typical for BV-2 cells cultured under conventional 2D conditions, to a population dominated by multipolar phenotypes. Fibronectin or collagen type I significantly suppressed matrix-induced ramification. These cell culture experiments illustrate the dependency of cell shape on spatial distribution of potential adhesion sites.
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3D Matrix hydrogels support microglia to grow and maintain ramified morphology and enable microglial response tests to proinflammation stimulus.
“For example, 3D Matrix hydrogels were reported to support microglia to grow and maintain ramified morphology and enable the microglial response tests to proinflammation stimulus.24, 25”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [24]
Cites
Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain
Lawson, L. J., Perry, V. H., Dri, P., & Gordon, S. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90229-w · Cited by 2,045 · see citing works
Immortalization of murine microglial cells by a v-raf / v-myc carrying retrovirus
Blasi, E., Barluzzi, R., Bocchini, V., Mazzolla, R., & Bistoni, F. (1990) · Journal of Neuroimmunology · doi:10.1016/0165-5728(90)90073-v · Cited by 1,075 · see citing works
Cytology & cellular pathology of the nervous system
Penfield, W. G. (1965) · Medical Entomology and Zoology · Cited by 1,035 · see citing works
Fibroblast biology in three-dimensional collagen matrices
Grinnell, F. (2003) · Trends in Cell Biology · doi:10.1016/s0962-8924(03)00057-6 · Cited by 819 · see citing works
Role of Microglia in Central Nervous System Infections
Rock, R. B., Gekker, G., Hu, S., Sheng, W. S., Cheeran, M., Lokensgard, J. R., & Peterson, P. K. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.4.942-964.2004 · Cited by 723 · see citing works
The origin and nature of ramified and amoeboid microglia: A historical review and current concepts
Ling, E., & Wong, W.-C. (1993) · Glia · doi:10.1002/glia.440070105 · Cited by 690 · see citing works
Ameboid microglia as effectors of inflammation in the central nervous system
Giulian, D. (1987) · Journal of Neuroscience Research · doi:10.1002/jnr.490180123 · Cited by 482 · see citing works
Brain macrophages: evaluation of microglia and their functions
Thomas, W. E. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90007-9 · Cited by 441 · see citing works
Microglia: activation and their significance in the central nervous system
Nakajima, K., & Kohsaka, S. (2001) · Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a002969 · Cited by 371 · see citing works
Lefcort, F. B., Venstrom, K., McDonald, J. A., & Reichardt, L. F. (1992) · Development · doi:10.1242/dev.116.3.767 · Cited by 188 · see citing works
The Extracellular Matrix and Cytokines Regulate Microglial Integrin Expression and Activation
Milner, R., & Campbell, I. L. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.7.3850 · Cited by 179 · see citing works
Jones, L. L., & Tuszynski, M. H. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-11-04611.2002 · Cited by 166 · see citing works
van Horssen, J., Bø, L., Vos, C. M. P., Virtanen, I., & de Vries, H. E. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000173894.09553.13 · Cited by 129 · see citing works
Increased Morphological Diversity of Microglia in the Activated Hypothalamic Supraoptic Nucleus
Ayoub, A. E., & Salm, A. K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-21-07759.2003 · Cited by 122 · see citing works
Extracellular Matrix Influences the Biogenesis of Amyloid Precursor Protein in Microglial Cells
Mönning, U., Banati, R. B., Masters, C. L., Sandbrink, R., Weidemann, A., & Beyreuther, K. T. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7104 · Cited by 74 · see citing works
Kiefer, R., Gold, R., Gehrmann, J., Lindholm, D., Wekerle, H., & Kreutzberg, G. W. (1993) · Journal of Neuroscience Research · doi:10.1002/jnr.490360405 · Cited by 55 · see citing works
Zierler, S., & Kerschbaum, H. (2005) · Brain Research · doi:10.1016/j.brainres.2005.01.086 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Del-Rio Hortega, 1932, Microglia, vol. 2, 481
Cited by
Sorted by citations
State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology
Alépée, N. (2014) · ALTEX · doi:10.14573/altex1406111 · Cited by 228 · see citing works
Biological and medical applications of a brain-on-a-chip
Pamies, D., Härtung, T., & Högberg, H. T. (2014) · Experimental Biology and Medicine · doi:10.1177/1535370214537738 · Cited by 121 · see citing works
Morphine enhances Tat-induced activation in murine microglia
Bokhari, S. M., Yao, H., Bethel-Brown, C. S., Fuwang, P., Williams, R., Dhillon, N. K., Hegde, R., Kumar, A., & Buch, S. J. (2009) · Journal of NeuroVirology · doi:10.1080/13550280902913628 · Cited by 84 · see citing works
Watson, P. M. D., Kavanagh, E., Allenby, G., & Vassey, M. (2017) · SLAS Discovery · doi:10.1177/2472555217691450 · Cited by 74 · see citing works
Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease
Cai, H., Ao, Z., Hu, L., Moon, Y., Wu, Z., Lu, H.-C., Kim, J., & Guo, F. (2020) · The Analyst · doi:10.1039/d0an01373k · Cited by 70 · see citing works
Functional Morphometric Analysis in Cellular Behaviors: Shape and Size Matter
Yu, H., Lim, K. P., Xiong, S., Tan, L. P., & SHIM, W. S. N. (2013) · Advanced Healthcare Materials · doi:10.1002/adhm.201300053 · Cited by 62 · see citing works
Modeling Immunity In Vitro: Slices, Chips, and Engineered Tissues
Hammel, J. H., Cook, S. R., Belanger, M. C., Munson, J. M., & Pompano, R. R. (2021) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-082420-124920 · Cited by 60 · see citing works
McHugh, D., Roskowski, D., Xie, S., & Bradshaw, H. B. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2013.00162 · Cited by 53 · see citing works
Seo, M., Kim, S., Kim, S., Zheng, L. T., Park, E. K., Lee, W., & Suk, K. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21552 · Cited by 40 · see citing works
Petralla, S., Chirico, F. D., Miti, A., Tartagni, O., Massenzio, F., Poeta, E., Virgili, M., Zuccheri, G., & Monti, B. (2021) · Biomolecules · doi:10.3390/biom11020306 · Cited by 37 · see citing works
Self-assembling peptide hydrogels promote microglial cells proliferation and NGF production
Chronopoulou, L., Togna, A. R., Guarguaglini, G., Masci, G., Giammaruco, F., Togna, G. I., & Palocci, C. (2012) · Soft Matter · doi:10.1039/c2sm25528f · Cited by 35 · see citing works
Korhonen, P., Malm, T., & White, A. R. (2018) · Neurochemistry International · doi:10.1016/j.neuint.2018.08.012 · Cited by 34 · see citing works
Honing the Double-Edged Sword: Improving Human iPSC-Microglia Models
Hedegaard, A., Stodolak, S., James, W., & Cowley, S. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.614972 · Cited by 31 · see citing works
Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation
Koss, K. M., Churchward, M. A., Jeffery, A. F., Mushahwar, V. K., Elias, A. L., & Todd, K. G. (2017) · Journal of Visualized Experiments · doi:10.3791/56615 · Cited by 16 · see citing works
Cho, H. J., Verbridge, S. S., Davalos, R. V., & Lee, Y. W. (2018) · Annals of Biomedical Engineering · doi:10.1007/s10439-018-2004-z · Cited by 15 · see citing works
Modeling Innate Antiviral Immunity in Physiological Context
Goldstein, M. E., & Scull, M. A. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167374 · Cited by 14 · see citing works
Cuní‐López, C., Stewart, R., White, A. R., & Quek, H. (2023) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2023.578017 · Cited by 9 · see citing works
Current methods for the microglia isolation: Overview and comparative analysis of approaches
Akhmetzyanova, E. R., Rizvanov, A. A., & Mukhamedshina, Y. O. (2023) · Cell and Tissue Research · doi:10.1007/s00441-023-03853-8 · Cited by 7 · see citing works
Current Methods for the Isolation and Cultivation of Microglia (Review)
Malinovskaya, N. A., Васильевна, Ф. О., Shishelova, K. O., & Panina, Y. A. (2021) · Современные технологии в медицине · doi:10.17691/stm2021.13.6.10 · Cited by 5 · see citing works
Hawkins, B. T., Hu, T., Dougherty, E. R., & Grego, S. (2016) · Applied In Vitro Toxicology · doi:10.1089/aivt.2016.0018 · Cited by 5 · see citing works
In vitro engineered models of neurodegenerative diseases
Morçimen, Z. G., Taşdemir, Ş., & Şendemir, A. (2024) · Biocell · doi:10.32604/biocell.2023.045361 · Cited by 4 · see citing works
Research Progress on Neural Cell Culture Systems
Li, T., Qin, X., & Ao, Q. (2025) · Current Neuropharmacology · doi:10.2174/011570159x360193250219082312 · Cited by 4 · see citing works
Zhang, J., Lim, Y. W., Medina, A., Chen, Y.-C., Wang, Y. I., Carvajal, M. C., Ferrer, M., & Lee, E. M. (2026) · Communications Biology · doi:10.1038/s42003-026-10696-w · Cited by 1 · see citing works
Nanostructuration d'électrodes en interface avec le vivant
Bibari, O. (2012) · theses.fr (ABES) · doi:10.70675/8daf86fbz85fcz4007zb642zf9eb0cb769ed
- Authors
- Pöttler, M., Zierler, S., & Kerschbaum, H. H.
- Affiliations
- University of Salzburg (AT)
- Corresponding author
- Kerschbaum, Hubert H.
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 410
- Issue
- 2
- Pages
- 137-140
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1977167767
- Cited by
- 24
- References
- 17
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 2 · 2021: 4 · 2020: 2 · 2018: 2 · 2017: 2 · 2016: 1 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- microglia, 3D cell culture, cell morphology, ramified microglia, cell shape, extracellular matrix, fibronectin, type I collagen, poly-D-lysine, cell adhesion
- MeSH terms
- Animals, Cell Count, Cell Line, Extracellular Matrix, Fibronectins, Chi-Square Distribution, Microglia, Cell Culture Techniques, Collagen Type I, Mice
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