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|Publication type:||Article in scientific journal|
|Type of review:||Peer review (publication)|
|Title:||Enhancement of neuroglial extracellular matrix formation and physiological activity of dopaminergic neural cocultures by macromolecular crowding|
|Authors:||Vo, Andy N.|
Song, Min Jae
Boutin, Molly E.
|Publisher / Ed. Institution:||MDPI|
|Subjects:||Drug testing; Extracellular matrix; Human iPSC derived astrocyte and dopaminergic neurons; Macromolecular crowding; Cell differentiation; Coculture technique; Humans; Macromolecular substance; Cell culture technique; Extracellular matrix|
|Subject (DDC):||610.28: Biomedicine, biomedical engineering|
|Abstract:||The neuroglial extracellular matrix (ECM) provides critical support and physiological cues for the proper growth, differentiation, and function of neuronal cells in the brain. However, in most in vitro settings that study neural physiology, cells are grown as monolayers on stiff surfaces that maximize adhesion and proliferation, and, therefore, they lack the physiological cues that ECM in native neuronal tissues provides. Macromolecular crowding (MMC) is a biophysical phenomenon based on the principle of excluded volume that can be harnessed to induce native ECM deposition by cells in culture. Here, we show that MMC using two species of Ficoll with vitamin C supplementation significantly boosts deposition of relevant brain ECM by cultured human astrocytes. Dopaminergic neurons cocultured on this astrocyte-ECM bed prepared under MMC treatment showed longer and denser neuronal extensions, a higher number of pre ad post synaptic contacts, and increased physiological activity, as evidenced by higher frequency calcium oscillation, compared to standard coculture conditions. When the pharmacological activity of various compounds was tested on MMC-treated cocultures, their responses were enhanced, and for apomorphine, a D2-receptor agonist, it was inverted in comparison to control cell culture conditions, thus emulating responses observed in in vivo settings. These results indicate that macromolecular crowding can harness the ECM-building potential of human astrocytes in vitro forming an ultra-flat 3D microenvironment that makes neural cultures more physiological and pharmacological relevant.|
|Further description:||Swissnex Austausch|
|Fulltext version:||Published version|
|License (according to publishing contract):||CC BY 4.0: Attribution 4.0 International|
|Departement:||Life Sciences and Facility Management|
|Organisational Unit:||Institute of Chemistry and Biotechnology (ICBT)|
|Appears in collections:||Publikationen Life Sciences und Facility Management|
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|2022_Vo-etal_Enhancement-neuroglial_extracellular-matrix-formation-macromolecular-crowding _MDPI.pdf||6.88 MB||Adobe PDF|
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Vo, A. N., Kundu, S., Strong, C., Jung, O., Lee, E., Song, M. J., Boutin, M. E., Raghunath, M., & Ferrer, M. (2022). Enhancement of neuroglial extracellular matrix formation and physiological activity of dopaminergic neural cocultures by macromolecular crowding. Cells, 11(14), 2131. https://doi.org/10.3390/cells11142131
Vo, A.N. et al. (2022) ‘Enhancement of neuroglial extracellular matrix formation and physiological activity of dopaminergic neural cocultures by macromolecular crowding’, Cells, 11(14), p. 2131. Available at: https://doi.org/10.3390/cells11142131.
A. N. Vo et al., “Enhancement of neuroglial extracellular matrix formation and physiological activity of dopaminergic neural cocultures by macromolecular crowding,” Cells, vol. 11, no. 14, p. 2131, 2022, doi: 10.3390/cells11142131.
Vo, Andy N., et al. “Enhancement of Neuroglial Extracellular Matrix Formation and Physiological Activity of Dopaminergic Neural Cocultures by Macromolecular Crowding.” Cells, vol. 11, no. 14, 2022, p. 2131, https://doi.org/10.3390/cells11142131.
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