Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Stem Cell Rev Rep. 2018 Apr;14(2):236-246. doi: 10.1007/s12015-017-9788-3.
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.
微小 RNA（miRs）是多形性成胶质细胞瘤（GBM）的潜在治疗靶点，但将其递送至肿瘤靶细胞的相关困难阻碍了它们的广泛应用。间充质干细胞（MSCs）可以迁移到包括 GBM 在内的癌症部位，并发挥抗肿瘤作用。在这项研究中，表明牙髓间充质干细胞（WJ-MSCs）具有将外源性 miR 递送至 GBM 细胞的能力，并对这种递呈的功能影响进行了特征描述。结果发现，以 miR-124 为例的标记 miR 可以通过依赖或外泌体非依赖的过程，与 WJ-MSCs 一起成功递送至 U87 GBM 细胞。研究表明，递呈的外源性 miR-124 显著降低了靶基因 CDK6 的荧光素酶活性。此外，递呈的 miR-124 增强了 GBM 细胞对替莫唑胺的化疗敏感性，并减少了 GBM 细胞的迁移。这些结果表明，使用 WJ-MSCs 衍生的外泌体进行外源性 miRNA 递呈可能为 GBM 癌症的 miRNA 替代治疗提供一种新方法。
