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Updated: Jul 23, 2025
Coculture Assays to Study Macrophage and Microglia Stimulation of Glioblastoma Invasion
Published on: October 20, 2016
Astrocytic scar restricting glioblastoma via glutamate-MAO-B activity in glioblastoma-microglia assembloid
Yen N Diep1,2,3, Hee Jung Park4, Joon-Ho Kwon5,6
1Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Background:
Glial scar formation is a reactive glial response confining injured regions in a central nervous system. However, it remains challenging to identify key factors formulating glial scar in response to glioblastoma (GBM) due to complex glia-GBM crosstalk.
Methods:
Here, we constructed an astrocytic scar enclosing GBM in a human assembloid and a mouse xenograft model. GBM spheroids were preformed and then co-cultured with microglia and astrocytes in 3D Matrigel. For the xenograft model, U87-MG cells were subcutaneously injected to the Balb/C nude female mice.
Results:
Additional glutamate was released from GBM-microglia assembloid by 3.2-folds compared to GBM alone. The glutamate upregulated astrocytic monoamine oxidase-B (MAO-B) activity and chondroitin sulfate proteoglycans (CSPGs) deposition, forming the astrocytic scar and restricting GBM growth. Attenuating scar formation by the glutamate-MAO-B inhibition increased drug penetration into GBM assembloid, while reducing GBM confinement.
Conclusions:
Taken together, our study suggests that astrocytic scar could be a critical modulator in GBM therapeutics.
