Differentiation Induction and Proliferation Inhibi-tion by A Cell-Free Approach for Delivery of Exogenous miRNAs to Neuroblastoma Cells by Mesenchymal Stem Cells

Background: Neuroblastoma (NB) is one of the most frequent malignant solid tumors in infancy and childhood, accounting for 15% of pediatric cancer deaths. Defective differentiation in neural crest cell precursors of sympathetic nervous system causes NB. Recently, the approach of differentiation therapy has shown considerable promise ineffective treatment of NB patients. MiR-124 is a kind of nervous system-specific miRNA that increases during neuronal differentiation and may be one of the potential therapeutic targets in the treatment of NB. How-ever, despite its well-established therapeutic potential, its ef-ficient delivery to the targeted tumor cells is a challenging task. Mesenchymal stem cells (MSCs) are multipotent adult progeni-tor cells that are also reported to have antitumor effects and the capability of migrating toward cancer cells and tumors Materials and Methods: In this study co cultured hAD MSCs and M17 NB Cells, then after 72 hours, the M17 NB cells were collected and flow cytometric analysis was used to detect the delivery of miR-124-Cy3 to M17 cells. Apoptosis induction in the treated M17 cells with transfer miR-124 and control miR was measured using the TUNEL kits.Results: In this study, it is shown that human adipocyte-MSCs (hAD-MSCs) have the ability to deliver exogenous miRNAs to NB cells. A specific kind of miRNA, i.e. miR-124, is success-fully delivered with hAD-MSCs to M17 NB cells via direct or indirect (exosome-based) contacts. It is demonstrated that the indirectly delivered miR-124 significantly decreases the prolif-eration of NB cells and induces their differentiation.Conclusion: These results offer the opportunity to use the delivered exogenous miRNAs by the derived exosomes from hAD-MSCs as a novel cell-free stem cell-based therapy for NB cancer.

Keywords:

Neuroblastoma , MiR-124 , Exosome , Mesenchymal Stem Cells , Differentiation