Placenta-derived mesenchymal stem cells and their secreted exosomes inhibit the self-renewal and stemness of glioma stem cells in vitro and in vivo

4^th World Congress on Cancer Science & Therapy

October 20-22, 2014 DoubleTree by Hilton Hotel Chicago-North Shore Conference Center, USA

Chaya Brodie, Efrat Buchris, Susan Finnis, Simona Cazacu, Cunli Xiang, Hae Kyung Lee and Laila Poisson

Accepted Abstracts: J Cancer Sci Ther

Abstract :

Mesenchymal stromal cells (MSCs) can be obtained from various sources, easily expanded in vitro for therapeutic applications and their safety and therapeutic impact have been demonstrated in various pre-clinical and clinical studies. MSCs have been shown to cross the blood brain barrier and migrate to sites of experimental GBM and can deliver cytotoxic compounds that exert antitumor effects. Here, we examined the effects of placenta-derived MSCs and their secreted exosomes on GSC stemness and oncogenic potential in vitro and in vivo. Placenta MSC-derived exosomes decreased the self-renewal, stemness markers, Nanog and Oct4 and the migration of these cells. Similarly, intracranial administration of the MSCs decreased the tumor volume of GSC-derived xenografts and prolonged animal survival. miRNA sequence analysis of placenta MSC-derived exosomes revealed a set of specific miRNAs that were downregulated in GSCs and that acted as tumor suppressors in these cells. We demonstrated delivery of some of these miRNAs to GSCs following treatments with MSC-derived exosomes. We further demonstrated that MSCs or exosomes that were loaded with exogenous miR-124 delivered high levels of this miRNA into glioma cells as detected by a novel quantitative miRNA reporter. Moreover, administration of placenta MSCs loaded with exogenous miR-124 exerted a strong inhibitory effect on GSC-derived xenograft growth. These results demonstrate that placenta-derived MSCs may have important clinical applications in stem cell-based glioma therapeutics. Moreover, these studies provide a novel approach for the targeted delivery of endogenous and exogenous anti-tumor miRNAs to glioma cells as a miRNA replacement therapy for GBM.

Biography :

Chaya Brodie has completed her PhD at 1998 from Bar-Ilan University and postdoctoral studies at University of Colorado and National Jewish Center for Immunology and Respiratory Medicine. She is a Senior Staff Scientists at the Henry Ford Hospital and a Professor in the Faculty of Life Sciences, Bar-Ilan University, Israel. She has published more than 135 papers in reputed journals and has been serving as a reviewer in various NIH study sections and in international foundations and societies.