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

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

  • Biomater Res. 2023 Jul 19;27(1):71. doi: 10.1186/s40824-023-00408-4.
Yen N Diep # 1 2 3,  Hee Jung Park # 4,  Joon-Ho Kwon # 5 6,  Minh Tran 1 2 3,  Hae Young Ko 4,  Hanhee Jo 4,  Jisu Kim 4,  Jee-In Chung 4,  Tai Young Kim 5,  Dongwoo Kim 4,  Jong Hee Chang 7,  You Jung Kang 1 2,  C Justin Lee 8 9 10,  Mijin Yun 11,  Hansang Cho 12 13 14
Affiliations

Affiliations

  • 1 Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 2 Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 3 Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 4 Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea.
  • 5 Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126, Republic of Korea.
  • 6 Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, Ulsan, 44919, Republic of Korea.
  • 7 Department of Neurosurgery, Severance Hospital, Seoul, 120-752, Republic of Korea.
  • 8 Center for Cognition and Sociality, Institute for Basic Science, Daejeon, 34126, Republic of Korea. cjl@ibs.re.kr.
  • 9 Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, Ulsan, 44919, Republic of Korea. cjl@ibs.re.kr.
  • 10 Korea University-Korea Institute of Science and Technology, Graduate School of Convergence Technology, Korea University, Seoul, 136-701, Republic of Korea. cjl@ibs.re.kr.
  • 11 Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea. YUNMIJIN@yuhs.ac.
  • 12 Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
  • 13 Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
  • 14 Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea. h.cho@g.skku.edu.
  • # Contributed equally.
PMID: 37468961 DOI: 10.1186/s40824-023-00408-4
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.

Keywords

Assembloid; Glial scar formation; Glioblastoma; Glutamate; MAO-B; Microglia.

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