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

Biomaterials Research

Research Article

Tai Young Kim¹  Joon-Ho Kwon²  C. Justin Lee³  Jong Hee Chang⁴  Hee Jung Park⁵  Hanhee Jo⁵  Jisu Kim⁵  Hae Young Ko⁵  Jee-In Chung⁵  Dongwoo Kim⁵  Mijin Yun⁵  You Jung Kang⁶  Yen N. Diep⁷  Minh Tran⁷  Hansang Cho⁷ 

[1] Center for Cognition and Sociality, Institute for Basic Science, 34126, Daejeon, Republic of Korea;Center for Cognition and Sociality, Institute for Basic Science, 34126, Daejeon, Republic of Korea;Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, 44919, Ulsan, Republic of Korea;Center for Cognition and Sociality, Institute for Basic Science, 34126, Daejeon, Republic of Korea;Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, 44919, Ulsan, Republic of Korea;Korea University-Korea Institute of Science and Technology, Graduate School of Convergence Technology, Korea University, 136-701, Seoul, Republic of Korea;Department of Neurosurgery, Severance Hospital, 120-752, Seoul, Republic of Korea;Department of Nuclear Medicine, Yonsei University College of Medicine, 03722, Seoul, Republic of Korea;Institute of Quantum Biophysics, Sungkyunkwan University, 16419, Suwon, Republic of Korea;Department of Biophysics, Sungkyunkwan University, 16419, Suwon, Republic of Korea;Institute of Quantum Biophysics, Sungkyunkwan University, 16419, Suwon, Republic of Korea;Department of Biophysics, Sungkyunkwan University, 16419, Suwon, Republic of Korea;Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 16419, Suwon, Republic of Korea;

关键词: Glial scar formation;    MAO-B;    Glutamate;    Glioblastoma;    Microglia;    Assembloid;   

DOI  :  10.1186/s40824-023-00408-4

 received in 2023-02-18, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundGlial 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.MethodsHere, 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.ResultsAdditional 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.ConclusionsTaken together, our study suggests that astrocytic scar could be a critical modulator in GBM therapeutics.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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