Delivery of Exogenous miR-124 to Glioblastoma Multiform Cells by Wharton’s Jelly Mesenchymal Stem Cells Decreases Cell Proliferation and Migration, and Confers Chemosensitivity
- 253 Downloads
MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme (GBM), but the difficulties associated with their delivery to tumor target cells have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM and exert anti-tumor effects. In this study, it is shown that Wharton’s jelly-MSCs (WJ-MSCs) have the ability to deliver exogenous miRs to GBM cells and the functional impact of this delivery is characterized. It is found that the labeled miR-124, as an example for miR of interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via dependent or exosome-independent processes. It is demonstrated that the delivered exogenous miR-124 significantly decreases the luciferase activity of the target gene CDK6. In addition, the delivered miR-124 enhances the chemosensitivity of GBM cells to temozolomide and decreases the migration of GBM cells. These results suggest that the use of exogenous miRNA delivery with the derived exosomes from WJ-MSCs may provide a novel approach for miRNA replacement therapy in GBM cancers.
KeywordsGlioma MiR-124 Temozolomide Mesenchymal stem cells Warton’s jelly
This work is a part of PhD thesis of Samaneh Sharif that is financially supported by the Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Compliance with Ethical Standards
The authors indicate no potential conflicts of interest. All the authors have materially participated in the research and the article preparation and have approved the final article.
Informed consent was obtained from all individual participants included in the study.
- 4.Louis, D., Posner, J., Jacobs, T., & Kaplan, R. (2000). Report of the brain tumor progress review group. Leesburg: National Institute of Neurological Disorders and Stroke, pp. 1–96.Google Scholar
- 7.Abba, M., Mudduluru, G., & Allgayer, H. (2012). MicroRNAs in cancer: small molecules, big chances. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents), 12, 733–743.Google Scholar
- 20.Kim, D. W., Staples, M., Shinozuka, K., Pantcheva, P., Kang, S. D., & Borlongan, C. V. (2013). Wharton’s jelly-derived mesenchymal stem cells: phenotypic characterization and optimizing their therapeutic potential for clinical applications. International Journal of Molecular Sciences, 14, 11692–11712.CrossRefPubMedPubMedCentralGoogle Scholar
- 23.Ng, F., Boucher, S., Koh, S., et al. (2008). PDGF, TGF-β, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood, 112, 295–307.CrossRefPubMedGoogle Scholar
- 31.Karussis, D., Kassis, I., Kurkalli, B. G. S., & Slavin, S. (2008). Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): a proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. Journal of the Neurological Sciences, 265, 131–135.CrossRefPubMedGoogle Scholar
- 42.Munoz, J. L., Bliss, S. A., Greco, S. J., Ramkissoon, S. H., Ligon, K. L., & Rameshwar, P. (2013). Delivery of functional anti-miR-9 by mesenchymal stem cell–derived exosomes to glioblastoma multiforme cells conferred chemosensitivity. Molecular Therapy—Nucleic Acids, 2, e126.CrossRefPubMedPubMedCentralGoogle Scholar