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

IF 11.3 1区医学 Q1 Medicine

Biomaterials Research Pub Date : 2023-07-19 DOI:10.1186/s40824-023-00408-4

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

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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.

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星形细胞疤痕通过谷氨酸- mao - b在胶质母细胞瘤-小胶质细胞集合体中的活性限制胶质母细胞瘤。

背景:神经胶质瘢痕形成是一种限制中枢神经系统损伤区域的反应性神经胶质反应。然而，由于胶质母细胞瘤与胶质母细胞瘤之间的复杂串扰，确定胶质母细胞瘤(GBM)中形成胶质瘢痕的关键因素仍然具有挑战性。方法:在此，我们构建了包裹GBM的星形细胞疤痕，并将其置于人组装体和小鼠异种移植模型中。将胶质母细胞瘤球体与小胶质细胞和星形胶质细胞在三维基质中共培养。对于异种移植模型，将U87-MG细胞皮下注射到Balb/C裸雌性小鼠。结果:与单独的GBM相比，GBM-小胶质细胞聚集体释放的谷氨酸增加了3.2倍。谷氨酸- mao - b抑制瘢痕形成增加了药物对GBM组装体的渗透，同时减少了GBM的限制。结论:综上所述，我们的研究表明星形细胞疤痕可能是GBM治疗的关键调节剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomaterials Research Medicine-Medicine (miscellaneous)

CiteScore

10.20

自引率

3.50%

发文量

审稿时长

30 days

期刊介绍： Biomaterials Research, the official journal of the Korean Society for Biomaterials, is an open-access interdisciplinary publication that focuses on all aspects of biomaterials research. The journal covers a wide range of topics including novel biomaterials, advanced techniques for biomaterial synthesis and fabrication, and their application in biomedical fields. Specific areas of interest include functional biomaterials, drug and gene delivery systems, tissue engineering, nanomedicine, nano/micro-biotechnology, bio-imaging, regenerative medicine, medical devices, 3D printing, and stem cell research. By exploring these research areas, Biomaterials Research aims to provide valuable insights and promote advancements in the biomaterials field.