Study of the role of microRNAs-encapsulated in extracellular vesicles in osteosarcoma

The tumor microenvironment is crucial in tumor progression, significantly
influenced by secreted factors like extracellular vesicles (EVs). In osteosarcoma
(OS), EVs play a role in promoting tumor growth and invasion. Additionally, EVs
derived from bone marrow mesenchymal stem cells (BMSCs) regulate cell
proliferation, migration, and survival, contributing to OS drug resistance.
Conversely, EVs from adipose-derived stem cells (ASCs) have been shown to
reduce OS cell proliferation.
Our study aims to elucidate the impact of ASC-EVs on OS growth and develop a
technology that enhances their therapeutic potential by modifying their surface
and cargo.
To explore the therapeutic potential of miRNAs encapsulated in isolated EVs, we
conducted functional assays on OS cells transfected with five specific miRNAs*.
Our findings suggest these miRNAs may act as tumor suppressors by inhibiting
OS cell migration and proliferation. Additionally, co-culture experiments were
performed to assess the effects on microenvironmental components by indirectly
co-culturing miRNA-transfected OS cells with fibroblasts and endothelial cells.
The results indicate that this co-culture significantly influences the migratory
behavior of fibroblasts and endothelial cells in an angiogenic environment.
Future studies will further investigate the therapeutic potential of miRNAencapsulated EVs on OS cells. We are also exploring the efficacy of ASC-EVs
with surface modifications achieved through peptide* grafting, showing promising
effects on cell viability.
Our findings highlight the potential of cultivating ASCs in a three-dimensional
scaffold-free extracellular matrix to enrich miRNAs within EVs, enhancing their
anti-tumor activity. Future research will focus on assessing the clinical viability of
using these EVs in treating osteosarcoma, paving the way for innovative
therapeutic strategies against this challenging bone malignancy.
*Names are withheld due to patent and publication considerations.