Cancer stem cells (CSCs) use their stemness properties to perpetuate their lineage and survive chemotherapy. Currently cell-based and cell-free therapies are under investigation to develop novel anti-cancer treatment modalities. We designed this study to investigate how cell extracts of mesenchymal stem cells affect the growth of glioma stem cells in vitro. Gliospheres were generated from the U87MG cell line and treated with conditioned media of Wharton's jelly and bone marrow mesenchymal stem cells. The effects were investigated at the functional and molecular levels. Our results showed that conditioned media from both types of mesenchymal stem cells changed the morphology of spheres and inhibited the proliferation, invasion, and self-renewal ability of glioma stem cells. At the molecular level, metabolism interruption at oxidative phosphorylation, cell cycle arrest, cell differentiation, and upregulation of the immune response were observed. Furthermore, this effect was mediated by the upregulation of the DKK1 gene inhibiting the Wnt pathway mediated by growth factor activity and downregulation of the KITLG gene activated by growth factor and cytokine activity, inhibiting multiple pathways. We conclude that different types of mesenchymal stem cells possess antitumor properties and their paracrine factors, in combination with anti-immune modalities, can provide practical therapeutic targets for glioblastoma treatment.
Bibliographical noteKAUST Repository Item: Exported on 2021-02-05
Acknowledgements: We are thankful to all the participants and management team at the Cell Therapy Center for their continuous cooperation and funding support for this study. We extend our gratitude to Dr Noor Gammoh from the University of Edinburgh, whose valuable comments make the manuscript clear and presentable. The graphical abstract was created with BioRender (https://biorender.com/). Conceptualization and Design, N.A.; Methodology, N.A. and E.A.; Formal Analysis, N.A. and D.A.; Investigation, N.A. E.A. D. Ali, S.W. and B.A.; Resources, D.A.-H. ; Data Curation, W.A.; Writing – Original Draft, N.A.; Writing – Review & Editing, F.J.; Project Administration, H.J. and A.A.; Funding Acquisition, A.A. The authors declare no competing interests.