Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal
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Hae Kyung Lee1, Susan Finniss1, Simona Cazacu1, Efrat Bucris2, Amotz Ziv-Av2, Cunli Xiang1, Kevin Bobbitt3, Sandra A. Rempel4, Laura Hasselbach5, Tom Mikkelsen5 Shimon Slavin6 and Chaya Brodie1,2
1 Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI,
2 Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel,
3 Department of Public Health Sciences,
4 Barbara Jane Levy Laboratory of Molecular Neuro-Oncology,
5 Eugene & Marcia Applebaum Laboratory of Invasion & Molecular Therapeutics and
6 The international center for Cell Therapy and Cancer Immunotherapy (CTCI), Tel Aviv, Israel
Chaya Brodie, email:
Keywords: miRNA delivery, mesenchymal stem cells, glioma, exosomes
Received: February 12, 2013 Accepted: February 27, 2013 Published: February 28, 2013
MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their clinical use is hindered by lack of effective delivery mechanisms to tumor sites. Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we examined the ability of MSCs derived from bone marrow, adipose tissue, placenta and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma stem cells (GSCs). We examined the delivery of miR-124 and miR-145 mimics as glioma cells and GSCs express very low levels of these miRNAs. Using fluorescently labeled miRNA mimics and in situ hybridization, we demonstrated that all the MSCs examined delivered miR-124 and miR-145 mimics to co-cultured glioma cells and GSCs via gap junction–dependent and independent processes. The delivered miR-124 and miR-145 mimics significantly decreased the luciferase activity of their respected reporter target genes, SCP-1 and Sox2, and decreased the migration of glioma cells and the self-renewal of GSCs. Moreover, MSCs delivered Cy3-miR-124 mimic to glioma xenografts when administered intracranially. These results suggest that MSCs can deliver synthetic exogenous miRNA mimics to glioma cells and GSCs and may provide an efficient route of therapeutic miRNA delivery in vivo.
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