MicroRNA loaded extracellular vesicles inhibit tumor progression and microglial polarization in an organ-on-a-chip

An interesting paper from Kim and Rhee groups at Korea Basic Science Institute and Incheon National University co-culturing glioblastoma with microglial cells to investigate tumor progression and therapeutic effects of microRNAs. The authors loaded microRNA-124 into extracellular vesicles to delivery the microRNA to the tumor microenvironment.

The microRNA was used as a potential therapeutic agent to regulate the crosstalk between tumor and microglia (macrophages residing in Central Nervous System). The treatment inhibited the invasion of both cell types and resulted in more rounded, less invasive, morphology in both tumor and microglial cells. The cytokine profile also showed that after miRNA treatment, most tumor progression-related cytokines were down regulated except those that were associate with polarization of the microglia cells to M1 phenotype. Co-culture of these cells and NK cells treated with microRNA-124 recruited more NK cells into the microenvironment of the tumor. These treatment has shown promising anti-tumor effects by decreasing related tumor markers, improving NK cell infiltration and inhibiting of microglial polarization.

Strong points:
+ Investigation of different miRNA anti-tumor effects in different cell lines.
+ Different methods of miRNA delivery into cells.
+ Co-culture of glioblastoma cells with different immune cells

Negative points:
– The same old story, they used PDMS but performed no investigation of the EV absorption into PDMS.
– They had to refresh the media in the chips manually everyday although the co-culture was for 4 days.

Have any questions? Leave a comment below.

Link to paper: https://www.thno.org/v11p9687

Organ-on-a-chip, microphysiological systems, tumor, MicroRNA, drug delivery, Microglia, co-culture, extracellular vesicles, glioblastoma, cancer, invasion, morphology, cytokines, tumor microenvironment

This paper is reproduced under https://creativecommons.org/licenses/by/4.0/. The image of the chip was edited for better clarity, data in the table and text were compiled and interpreted by AZAR Innovations.

Hong S, You JY, Paek K, Park J, Kang SJ, Han EH, Choi N, Chung S, Rhee WJ, Kim JA. Inhibition of tumor progression and M2 microglial polarization by extracellular vesicle-mediated microRNA-124 in a 3D microfluidic glioblastoma microenvironment. Theranostics 2021; 11(19):9687-9704. doi:10.7150/thno.60851.