Bioengineered 3D Glial Cell Culture Systems and Applications for Neurodegeneration and Neuroinflammation
Open accessAbstract
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures. Given the complexity of the environment from which cells originate, and their various cell-cell and cell-matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery. 3D cell models have now been developed for almost all CNS cell types, including neurons, astrocytes, microglia, and oligodendrocyte cells. This review will highlight a number of current and emerging techniques for the culture of astrocytes and microglia, glial cell types with a critical role in neurodegenerative and neuroinflammatory conditions. We describe recent advances in glial cell culture using electrospun polymers and hydrogel macromolecules, and highlight how these novel culture environments influence astrocyte and microglial phenotypes in vitro, as compared to traditional 2D systems. These models will be explored to illuminate…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Microglia cultured in 2D settings show dramatically different morphology and phenotype compared with that in vivo.
“However, microglia cultured in such a 2D settings show dramatically different morphology and phenotype as compared with that in vivo.”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [17]
Microglia display a ramified morphology in 3D brain tissues, while 2D cultured microglia tend to show an amoeboid morphology with an increased expression of proinflammatory and motility genes related to microglia activation.
“Microglia display a ramified morphology in 3D brain tissues, while the 2D cultured microglia tend to show an amoeboid morphology with an increased expression of proinflammatory and motility genes that are related to microglia activation.17”
From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [17]
Cites
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372 · see citing works
Astrocytes: Biology and pathology
Sofroniew, M. V., & Vinters, H. V. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0619-8 · Cited by 5,196 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · see citing works
Modeling Development and Disease with Organoids
Clevers, H. (2016) · Cell · doi:10.1016/j.cell.2016.05.082 · Cited by 3,196 · see citing works
Cahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129 · see citing works
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
The International Multiple Sclerosis Genetics Consortium & The Wellcome Trust Case Control Consortium 2 (2011) · Nature · doi:10.1038/nature10251 · Cited by 2,697 · see citing works
Identification of a unique TGF-β–dependent molecular and functional signature in microglia
Butovsky, O., Jedrychowski, M. P., Moore, C. S., Cialic, R., Lanser, A. J., Gabriely, G., Koeglsperger, T., Dake, B., Wu, P. M., Doykan, C. E., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3599 · Cited by 2,543 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
How neuroinflammation contributes to neurodegeneration
Ransohoff, R. M. (2016) · Science · doi:10.1126/science.aag2590 · Cited by 1,967 · cited 1× · see citing works
“Glial inflammatory genes, the innate immune system, and neuroinflammation in particular are currently highly active areas of academic research.(30) All of the above have spurred a resurgence in interest from pharmaceutical and biotechnology companies in astrocytes and microglia as target cell types for high-throughput…”
BackgroundHow were new medicines discovered?
Swinney, D. C., & Anthony, J. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3480 · Cited by 1,812 · see citing works
Innate immune activation in neurodegenerative disease
Heneka, M. T., Kummer, M. P., & Latz, E. (2014) · Nature Reviews Immunology · doi:10.1038/nri3705 · Cited by 1,437 · see citing works
Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease
Prinz, M., & Priller, J. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3722 · Cited by 1,329 · see citing works
A three-dimensional human neural cell culture model of Alzheimer’s disease
Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D’Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., et al. (2014) · Nature · doi:10.1038/nature13800 · Cited by 1,195 · see citing works
Three-dimensional culture systems in cancer research: Focus on tumor spheroid model
Nath, S., & Devi, G. R. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.03.013 · Cited by 919 · see citing works
Sofroniew, M. V. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020420 · Cited by 695 · see citing works
Microglia: Dynamic Mediators of Synapse Development and Plasticity
Wu, Y., Dissing-Olesen, L., MacVicar, B. A., & Stevens, B. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.08.008 · Cited by 661 · see citing works
Raja, W. K., Mungenast, A. E., Lin, Y.-T., Ko, T., Abdurrob, F., Seo, J., & Tsai, L.-H. (2016) · PLOS ONE · doi:10.1371/journal.pone.0161969 · Cited by 569 · see citing works
New insights on the role of microglia in synaptic pruning in health and disease
Hong, S., Dissing-Olesen, L., & Stevens, B. (2016) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2015.12.004 · Cited by 557 · see citing works
Factors regulating microglia activation
Kierdorf, K., & Prinz, M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00044 · Cited by 360 · see citing works
Biomimetic 3D tissue models for advanced high-throughput drug screening
Nam, K.-H., Smith, A. S. T., Lone, S., Kwon, S., & Kim, D.-H. (2015) · SLAS Technology · doi:10.1177/2211068214557813 · Cited by 171 · see citing works
Schilling, T., Nitsch, R., Heinemann, U., Haas, D., & Eder, C. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01661.x · Cited by 108 · see citing works
Deciphering Resting Microglial Morphology and Process Motility from a Synaptic Prospect
Hristovska, I., & Pascual, O. (2016) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2015.00073 · Cited by 92 · see citing works
Min, S. K., Park, J. S., Luo, L., Kwon, Y. S., Lee, H. C., Jung Shim, H., Kim, I.-D., Lee, J.-K., & Shin, H. S. (2015) · Scientific Reports · doi:10.1038/srep14418 · Cited by 74 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Expanding and optimizing 3D bioprinting capabilities using complementary network bioinks
Ouyang, L., Armstrong, J. P. K., Lin, Y., Wojciechowski, J. P., Lee-Reeves, C., Hachim, D., Zhou, K., Burdick, J. A., & Stevens, M. M. (2020) · Science Advances · doi:10.1126/sciadv.abc5529 · Cited by 293 · see citing works
Microglial NLRP3 inflammasome activation in multiple sclerosis
(2020) · Advances in Protein Chemistry and Structural Biology · doi:10.1016/bs.apcsb.2019.08.007 · Cited by 83 · 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
An Overview of Multiple Sclerosis In Vitro Models
Czpakowska, J., Kałuża, M., Szpakowski, P., & Głąbiński, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147759 · Cited by 7 · see citing works
- Authors
- Watson, P. M. D., Kavanagh, E., Allenby, G., & Vassey, M.
- Affiliations
- Aurelia Bioscience (United Kingdom) (GB)
- Corresponding author
- Watson, P. Marc D.
- Vassey, Matthew
- ORCID
- Vassey, Matthew
- Venue
- SLAS Discovery
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 22
- Issue
- 5
- Pages
- 583-601
- ISSN
- 2472-5552 (ISSN-L)
- OpenAlex
- W2618956750
- Cited by
- 74
- References
- 23
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 15 · 2023: 7 · 2022: 5 · 2021: 15 · 2020: 9 · 2019: 4 · 2018: 7 · 2017: 3
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- SLAS DISCOVERY (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- 3D cell culture, glial cells, astrocytes, microglia, neurodegeneration, neuroinflammation, hydrogels, cell-matrix interactions, astrocyte phenotype, microglial phenotype, Alzheimer's disease, Parkinson's disease, stroke, traumatic brain injury, drug discovery models
- MeSH terms
- Astrocytes, Cell Communication, Cells, Cultured, Central Nervous System, Humans, Inflammation, Neuroglia, Neurons, Microglia, Cell Culture Techniques, Neurodegenerative Diseases, Bioengineering
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
