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Updated: Oct 17, 2025
Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Inhibition of tumor progression and M2 microglial polarization by extracellular vesicle-mediated microRNA-124 in a 3D
Soohyun Hong1,2,3, Jae Young You2,4, Kyurim Paek2,3
1Research Center for Bioconvergence Analysis, Korea Basic Science Institute, Chungbuk 28119, Republic of Korea.
Abstract:
Background: Glioblastoma (GBM) is one of the most aggressive types of brain cancer. GBM progression is closely associated with microglia activation; therefore, understanding the regulation of the crosstalk between human GBM and microglia may help develop effective therapeutic strategies. Elucidation of efficient delivery of microRNA (miRNA) via extracellular vesicles (EVs) and their intracellular communications is required for therapeutic applications in GBM treatment. Methods: We used human GBM cells (U373MG) and human microglia. MiRNA-124 was loaded into HEK293T-derived EVs (miR-124 EVs). Various anti-tumor effects (proliferation, metastasis, chemosensitivity, M1/M2 microglial polarization, and cytokine profile) were investigated in U373MG and microglia. Anti-tumor effect of miR-124 EVs was also investigated in five different patient-derived GBM cell lines (SNU-201, SNU-466, SNU-489, SNU-626, and SNU-1105). A three-dimensional (3D) microfluidic device was used to investigate the interactive microenvironment of the tumor and microglia. Results: MiR-124 EVs showed highly efficient anti-tumor effects both in GBM cells and microglia. The mRNA expression levels of tumor progression and M2 microglial polarization markers were decreased in response to miR-124 EVs. The events were closely related to signal transducer and activator of transcription (STAT) 3 signaling in both GBM and microglia. In 3D microfluidic experiments, both U373MG and microglia migrated to a lesser extent and showed less-elongated morphology in the presence of miR-124 EVs compared to the control. Analyses of changes in cytokine levels in the microfluidic GBM-microglia environment showed that the treatment with miR-124 EVs led to tumor suppression and anti-cancer immunity, thereby recruiting natural killer (NK) cells into the tumor. Conclusions: In this study, we demonstrated that EV-mediated miR-124 delivery exerted synergistic anti-tumor effects by suppressing the growth of human GBM cells and inhibiting M2 microglial polarization. These findings provide new insights toward a better understanding of the GBM microenvironment and provide substantial evidence for the development of potential therapeutic strategies using miRNA-loaded EVs.
Insights
Extracellular vesicles loaded with microRNA-124 (miR-124 EVs) show potent anti-tumor effects against glioblastoma (GBM) by suppressing GBM cell growth and M2 microglial polarization, offering a promising therapeutic strategy.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Extracellular Vesicles
- MicroRNA Therapeutics
Background:
- Glioblastoma (GBM) is an aggressive brain cancer where microglia activation significantly influences tumor progression.
- Understanding GBM-microglia crosstalk is crucial for developing effective therapeutic strategies.
- Efficient delivery of microRNA (miRNA) via extracellular vesicles (EVs) is needed for GBM treatment.
Purpose of the Study:
- To investigate the anti-tumor effects of miRNA-124 loaded into extracellular vesicles (miR-124 EVs) on human glioblastoma (GBM) cells and microglia.
- To explore the therapeutic potential of EV-mediated miRNA delivery in the GBM microenvironment.
Main Methods:
- Human GBM cells (U373MG) and microglia were treated with miR-124 EVs.
- Anti-tumor effects were assessed, including proliferation, metastasis, chemosensitivity, and microglial polarization.
- A 3D microfluidic device modeled the GBM-microglia interactive microenvironment.
Main Results:
- miR-124 EVs demonstrated significant anti-tumor effects on both GBM cells and microglia.
- Treatment decreased tumor progression markers and M2 microglial polarization, linked to STAT3 signaling.
- 3D microfluidic models showed reduced cell migration and altered morphology with miR-124 EVs, promoting anti-cancer immunity and NK cell recruitment.
Conclusions:
- EV-mediated delivery of miR-124 exerts synergistic anti-tumor effects by suppressing GBM growth and inhibiting M2 microglial polarization.
- These findings enhance understanding of the GBM microenvironment.
- miR-124 EVs represent a promising therapeutic strategy for glioblastoma treatment.
