방사선의학 웹진

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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.

Affiliations

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