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Anti-Oncogenic Activities Exhibited By Secretomes Of Mesenchymal Stem Cells Are Mediated By Modulation Of KITLG and DKK1 Genes In Glioma Stem Cells.

Background. Cancer stem cells (CSCs) use their stemness properties such as self renewal, toxicity, plasticity, and communication with the tumor microenvironment (TME) to perpetuate their lineage and survive chemotherapy. Learning how to interrupt the self renewal ability or modulate the interaction of CSCs with the TME signaling will dramatically improve therapeutic impact on patient’s remission. Antitumor properties of mesenchymal stem cells (MSCs) are currently under investigations and different approaches have been applied to gain bene cial effects However, different types of MSCs yielded different con icting results. In order to investigate if different types of MSCs preconditioned in the same culture conditions can exert alike anti oncogenic effect on glioma stem cells, we planned this study.
Methods. GSCs were isolated from U87 cell line by FACS cell sorter, characterized and established as gliospheres. Condition media from MSCs of Wharton Jelly (WJ-MSCs) and bone marrow (BM-MSCs) were harvested and used as treatments on glioshperes (3D) to investigate the effect on proliferation, invasion and self renewal properties of GSCs. Microarray analysis was used to determine the effect at molecular level. Speci c human CSC gene arrays were applied to validate the ndings of the microarray explicitly the pluripotency of the GSCs.
Results. Our results from functional and molecular assays showed that condition media (CM) from both types of MSCs inhibited the metabolism by interrupting oxidative phosphorylation, arrested the cell cycle, induced cell differentiation, targeted the pluripotency and up-regulated the immune response in GSCs …​