title: Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal.
abstract: 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.
authors.affiliation: Davidson Laboratory of Cell Signaling and Tumorigenesis, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Hospital, Detroit, MI, USA.
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Lee
authors.forename: Susan
authors.initials: S
authors.lastname: Finniss
authors.forename: Simona
authors.initials: S
authors.lastname: Cazacu
authors.forename: Efrat
authors.initials: E
authors.lastname: Bucris
authors.forename: Amotz
authors.initials: A
authors.lastname: Ziv-Av
authors.forename: Cunli
authors.initials: C
authors.lastname: Xiang
authors.forename: Kevin
authors.initials: K
authors.lastname: Bobbitt
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Rempel
authors.forename: Laura
authors.initials: L
authors.lastname: Hasselbach
authors.forename: Tom
authors.initials: T
authors.lastname: Mikkelsen
authors.forename: Shimon
authors.initials: S
authors.lastname: Slavin
authors.forename: Chaya
authors.initials: C
authors.lastname: Brodie
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D018920:Coculture Techniques; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000008:administration & dosage* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C509207:MIRN124 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs
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