Characterization and Antiproliferative Activity of Glioma-Derived Extracellular Vesicles

Abstract

Aim: To characterize a method to isolate glioma-derived extracellular vesicles (GEVs) and understand their role in immune system modulation and glioma progression. Materials & methods: GEVs were isolated by differential centrifugation from C6 cell supernatant and characterized by size and expression of CD9, HSP70, CD39 and CD73. The glioma model was performed by injecting C6 glioma cells into the right striatum of Wistar rats in the following groups: controls (C6 cells alone), coinjection (C6 cells + GEVs) and GEVs by intranasal administration followed by immune cells, tumor size and cells proliferation analyses. Results: GEVs presented uniform size (175 nm), expressed CD9, HSP70, CD39, CD73 and produced adenosine. In vivo, we observed a reduction in tumor size, in cell proliferation (Ki-67) and in a regulatory cell marker (FoxP3). Conclusion: GEVs, administered before or at tumor challenge, have antiproliferative properties and reduce regulatory cells in the glioma microenvironment.

Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

“…Delivery of MSC-derived EVs to the CNS has been described in several studies [ 128 , 129 , 130 , 131 , 132 ]. In line with these findings, Scholl et al, [ 133 ] described the intranasal delivery of glioma-derived EVs obtained in vitro to glioma tissue in rats. The advantages of this administration route may be particularly important in the treatment of neurodegenerative disorders [ 134 ].…”

Neuroprotection from Stem Cell-Derived Human Adipose Extracellular Vesicles Intranasally Administered 24 Hours After Stroke in Rats. 

“…The isolation was completed by centrifugation (100,000×g at 4 °C for 2 h). The supernatant was discarded, PBS was used to wash the pellet containing EVs, and the cell suspension was centrifuged at 100,000×g at 4 °C for 2 h [41]. Finally, the pellet was resuspended in 100 µL of PBS and stored at -20°C [38].…”

Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma

“…For example, in 2020 the research group led by Fabrício Figueiró demonstrated that glioma-derived extracellular vesicles expressing CD9, HSP70, CD39, and CD73, and producing adenosine, reduced glioma progression by modulating the tumor microenvironment. Thereby, a reduction in tumor size occurred by acting on cell proliferation [85].…”