DataVXBiomaterials ResearchPaper
journal article·2023-02-09Open access

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

Yen N. Diep, Hee Jung Park, Joon-Ho Kwon, Minh Tran, Hae Young Ko, Hanhee Jo, Jisu Kim, Jee-In Chung, Tai Young Kim, Dongwoo Kim, Jong Hee Chang, You Jung Kang, C. Justin Lee, Mijin Yun, Hansang Cho

Biomaterials Research· Volume 27· Issue 1
Publisher pageOpen full text
Source abstract

Abstract

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
Source: crossref · Quality: baseline

Research context

Materials processing

OpenAlex topics: Glioma Diagnosis and Treatment · Neurogenesis and neuroplasticity mechanisms · Nerve injury and regeneration

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Quantum Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Department of Biophysics, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Department of Nuclear Medicine, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, Republic of Korea.

Department of Biomedical Engineering, Ulsan National Institute of Science & Technology, Ulsan 44919, Republic of Korea.

Department of Neurosurgery, Severance Hospital, Seoul 120-752, Republic of Korea.

Korea University-Korea Institute of Science and Technology, Graduate School of Convergence Technology, Korea University, Seoul 136-701, Republic of Korea.

Funding

National Research Foundation of Korea · Ministry of Health & Welfare and Ministry of Science · Korea Health Industry Development Institute · Center for Cognition and Sociality

References (42)

Show source-provided references
1. 10.1038/s41467-019-11707-710.1038/s41467-019-11707-7 ↗
2. 10.1016/j.neures.2017.10.00410.1016/j.neures.2017.10.004 ↗
3. 10.1038/nm.435410.1038/nm.4354 ↗
4. 10.1038/s41467-019-08446-010.1038/s41467-019-08446-0 ↗
5. 10.4103/1673-5374.35791210.4103/1673-5374.357912 ↗
6. Xia L, Qi J, Tang M, Liu J, Zhang D, Zhu Y, et al. Continual Deletion of Spinal Microglia Reforms Astrocyte Scar Favoring Axonal Regeneration. Front Pharmacol. 2022;13(June):1–10.
7. 10.1038/nature1397410.1038/nature13974 ↗
8. 10.1016/S0896-6273(00)80781-310.1016/S0896-6273(00)80781-3 ↗
9. 10.1523/JNEUROSCI.3547-03.200410.1523/JNEUROSCI.3547-03.2004 ↗
10. 10.1016/j.neuint.2019.10462810.1016/j.neuint.2019.104628 ↗
11. 10.1016/j.baga.2012.06.00610.1016/j.baga.2012.06.006 ↗
12. 10.1038/nm.363910.1038/nm.3639 ↗
13. 10.1371/journal.pone.000161610.1371/journal.pone.0001616 ↗
14. 10.1111/j.1745-7254.2006.00336.x10.1111/j.1745-7254.2006.00336.x ↗
15. 10.1074/jbc.M30637820010.1074/jbc.M306378200 ↗
16. 10.1002/glia.2411010.1002/glia.24110 ↗
17. 10.1016/j.celrep.2020.10786110.1016/j.celrep.2020.107861 ↗
18. 10.1016/j.cub.2019.11.07910.1016/j.cub.2019.11.079 ↗
19. 10.3389/fendo.2013.0019110.3389/fendo.2013.00191 ↗
20. 10.1523/JNEUROSCI.19-24-10767.199910.1523/JNEUROSCI.19-24-10767.1999 ↗
21. 10.1023/A:100642691765410.1023/A:1006426917654 ↗
22. 10.1038/nm.245310.1038/nm.2453 ↗
23. 10.3390/ijms2007179610.3390/ijms20071796 ↗
24. 10.1016/j.xpro.2021.10034510.1016/j.xpro.2021.100345 ↗
25. 10.1007/s13311-021-01097-410.1007/s13311-021-01097-4 ↗
26. 10.1523/JNEUROSCI.2121-13.201310.1523/JNEUROSCI.2121-13.2013 ↗
27. 10.3390/biomedicines903032410.3390/biomedicines9030324 ↗
28. 10.1097/RLU.000000000000434110.1097/RLU.0000000000004341 ↗
29. 10.1007/s00259-018-3948-910.1007/s00259-018-3948-9 ↗
30. 10.4161/cbt.2135310.4161/cbt.21353 ↗
31. Ricard C, Tchoghandjian A, Luche H, Grenot P, Figarella-Branger D, Rougon G, et al. Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma-bearing mice. Sci Rep. 2016;6(April):1–15.10.1038/srep26381 ↗
32. 10.1038/s41467-019-10493-610.1038/s41467-019-10493-6 ↗
33. 10.1093/intbio/zyaa01010.1093/intbio/zyaa010 ↗
34. 10.1038/s41598-021-96647-310.1038/s41598-021-96647-3 ↗
35. 10.1038/s41422-021-00528-310.1038/s41422-021-00528-3 ↗
36. Matias D, Balça-Silva J, da Graça GC, Wanjiru CM, Macharia LW, Nascimento CP, et al. Microglia/astrocytes–glioblastoma crosstalk: Crucial molecular mechanisms and microenvironmental factors. Front Cell Neurosci. 2018;12(August):1–22.10.3389/fncel.2018.00235 ↗
37. 10.3390/ijms2119715410.3390/ijms21197154 ↗
38. 10.1016/j.aanat.2019.15144010.1016/j.aanat.2019.151440 ↗
39. 10.1007/s11064-011-0701-110.1007/s11064-011-0701-1 ↗
40. 10.1158/0008-5472.CAN-16-231010.1158/0008-5472.CAN-16-2310 ↗
41. Pampliega O Domercq M Soria FN Villoslada P Rodríguez-antigüedad A Matute C. Increased expression of cystine/glutamate antiporter in multiple sclerosis. J Neuroinflammation. 2011;8:63. https://doi.org/10.1186/1742-2094-8-63.10.1186/1742-2094-8-63 ↗
42. 10.1016/j.lfs.2008.03.01010.1016/j.lfs.2008.03.010 ↗