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Astrocytic scar restricting glioblastoma via glutamate–MAO-B activity in glioblastoma-microglia assembloid

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Title
Astrocytic scar restricting glioblastoma via glutamate–MAO-B activity in glioblastoma-microglia assembloid
Author(s)
Diep, Yen N.; Park, Hee Jung; Joon‑Ho Kwon; Tran, Minh; Ko, Hae Young; Jo, Hanhee; Kim, Jisu; Chung, Jee-In; Tai Young Kim; Kim, Dongwoo; Chang, Jong Hee; Kang, You Jung; C. Justin Lee; Yun, Mijin; Cho, Hansang
Publication Date
2023-07
Journal
Biomaterials Research, v.27, no.1
Publisher
BioMed Central Ltd
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: [Figure not available: see fulltext.].
URI
https://pr.ibs.re.kr/handle/8788114/14300
DOI
10.1186/s40824-023-00408-4
ISSN
1226-4601
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > 1. Journal Papers (저널논문)
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