Delivery of miRNA to brain cancer cells by the secreted exosomes from mesenchymal stem cells as a new method of cancer therapy

Background and Aim: MicroRNAs (miRs) replacement therapy provide a novel approach for cancer treatment. However, the difficulties associated with miRs delivery to tumor target cells have hampered their widespread use. MiR-۱۲۴ is a kind of nervous system-specific miRNA that increases during neuronal development and may be one of the potential therapeutic targets in the treatment of brain cancers. As a novel cell-free stem cell-based therapy, genetically modified exosomes secreted from mesenchymal stem cells (MSCs) have yielded positive therapeutic results for delivery of miRs.The aim of the present study was to show that MSCs have the potential of delivering exogenous miRNAs to Nouroblastoma (NB) and Glioblastoma (GBM) cells to induce differentiation and decrease proliferation of these cells.Methods: In this experimental study, MSCs are isolated, cultured and differentiated. M۱۷ and U۸۷ (human NB and GBM) cells are also cultured. A specific kind of miRNA, i.e. miR-۱۲۴, is delivered successfully with the secreted exosomes from MSCs to M۱۷ and GBM cells.Results: It is shown that the delivered exogenous miR-۱۲۴ significantly decreases the CDK۶ gene in GBM and NB cells and hence, decreases the proliferation. In addition, the delivered miR-۱۲۴ induces the differentiation in NB cells and enhanced the chemosensivity of GBM cells to temozolomide.Conclusion: The results offer the opportunity to use the delivered exogenous miRs by the derived exosomes from MSCs as a potential cell-free stem cell-based therapy for NB and GBM cancers.

کلیدواژه ها:

Exosomes ، Glioblastoma ، Nouroblastoma ، miRNA ، Mesenchymal stem cells