Abstract
Abstract
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.
Graphical Abstract
Funder
National Research Foundation of Korea
Ministry of Health & Welfare and Ministry of Science
Korea Health Industry Development Institute
Center for Cognition and Sociality
Publisher
Springer Science and Business Media LLC
Subject
Biomedical Engineering,Biomaterials,Medicine (miscellaneous),Ceramics and Composites
Cited by
1 articles.
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