Biomaterials Research (Jul 2023)

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

DOI
https://doi.org/10.1186/s40824-023-00408-4
Journal volume & issue
Vol. 27, no. 1
pp. 1 – 19

Abstract

Read online

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

Keywords