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

Abstract

Objective: Neuroblastoma (NB) is one of the frequently observed malignant solid tumors of childhood and infancy, accounting for 15% of pediatric cancer deaths. Recently, the approach of differentiation therapy has shown considerable promise in effective treatment of NB patients. MiR-124 belongs to the nervous system-specific miRNAs that is increased during neuronal differentiation and may be one of the potential therapeutic targets for the treatment of NB. However, despite its well-established therapeutic potential, its efficient delivery to the targeted tumor cells is a challenging task. Mesenchymal stem cells (MSCs) are multipotent adult progenitor cells that have antitumor properties, and they can migrate to cancer cells and tumors. This study aimed to assess whether human adipose tissue-derived MSCs (hADMSCs) have the potential to deliver exogenous miRNAs to NB cells to induce differentiation and decrease proliferation of cancer cells. Materials and Methods: In this experimental study, hAD-MSCs were isolated, cultured, and differentiated. The M17 human NB cell line were also cultured. A specific type of miRNAs, i.e., miR-124 was successfully delivered to M17 NB cells with the aid of hAD-MSCs using the direct or indirect (exosome-based) contacts. Results: It was shown that indirect delivery of miR-124 considerably decreased the proliferation of NB cells and induced their differentiation. Conclusion: The results suggest the use of delivered exogenous miRNAs by the derived exosomes from hAD-MSCs as a novel cell-free stem cell-based therapy for NB cancer.

Keywords

• differentiation
• exosome
• mesenchymal stem cells
• mir-124
• neuroblastoma