한빛사논문
- 조회623
Yen N. Diep1,2,3†, Hee Jung Park4†, Joon‑Ho Kwon5,6†, Minh Tran1,2,3, Hae Young Ko4, Hanhee Jo4, Jisu Kim4, Jee‑In Chung4, Tai Young Kim5, Dongwoo Kim4, Jong Hee Chang7, You Jung Kang1,2, C. Justin Lee5,6,8*, Mijin Yun4* and Hansang Cho1,2,3*
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.
8Korea University-Korea Institute of Science and Technology, Graduate School of Convergence Technology, Korea University, Seoul 136‑701, Republic of Korea.
†Yen N. Diep, Hee Jung Park and Joon-Ho Kwon these authors contributed equally.
*Correspondence: C. Justin Lee, Mijin Yun, Hansang Cho
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.
논문정보
- Research article
- 2023년 07월 (BRIC 등록일 2023-08-03)
- 국내 연구진
- 바이오·의료융합 > 뇌인지과학
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