Stem cells and gliomas: past, present, and future
- 652 Downloads
The recognition of stem cells (SC) in the adult CNS and in association with gliomas has spawned an entire field of research and intense investigation. A large body of knowledge is being accumulated to gain insight into the pathobiology of gliomas with the intent of finally improving the grave prognosis that continues to beset patients with high grade gliomas (HGG). In this article, we provide a historical overview of the events leading to the discovery of SC and glioma stem cells (GSC). We then focus on the current understanding of GSC with respect to markers, clinical significance, and their targeting. We discuss current data and developments using SC as vehicles to delivery therapeutic agents to HGG. We conclude with a discussion of opportunities for future development and concepts aimed at reducing tumor recurrence and improving survival for patients with HGG.
KeywordsStem cells Glioma stem cells Cell therapy Gene therapy High grade glioma Glioblastoma Clinical trials
This work was supported, in part, by a grant from the National Institutes of Health/National Cancer Institute (RO1 CA1 129489-01A1 to I.M.G).
Conflict of interest
- 5.Virchow R (1863) Die krankhaften Geschwuelste. Hirshwald, BerlinGoogle Scholar
- 6.Germano IM, Swiss V, Casaccia P (2010) Primary brain tumors, neural stem cells, and brain tumor cancer cells: where is the link? Neuro-pharmacology 58(6):903–910Google Scholar
- 20.Rasper M, Schafer A, Piontek G et al (2010) Aldehyde dehydrogenase 1 positive glioblastoma cells show brain tumor stem cell capacity. Neurooncology 12:1024–1033Google Scholar
- 32.Raso A, Vecchio D, Cappelli E et al (2012) Characterization of glioma stem cells through multiple stem cell markers and their specific sensitization to double-strand break-inducing agents by pharmacological inhibition of ataxia telangiectasia mutated protein. Brain Pathol 22:677–688PubMedCrossRefGoogle Scholar
- 40.Kang KB, Zhu C, Wong YL et al (2012) Gefitinib radiosensitizes stem-like glioma cells: inhibition of epidermal growth factor receptor-Akt-DNA-PT signaling, accompanied by inhibition of DNA double-strand break repair. Int J Radiat Oncol Biol Phys 83:e43–e52. doi: 10.1016/j.ijrobp.2011.11.037 PubMedCrossRefGoogle Scholar
- 43.Asutkhar S, Velpula KK, Chetty C et al (2012) Epigenetic regulation of miRNA-211 by MMP-9 governs glioma cell apoptosis, chemosensitivity and radiosensitivity. Oncotarget 3:1439–1454Google Scholar
- 48.Germano IM, Binello E (2012) Stem cells as vehicles for the treatment of high-grade gliomas. Neurooncology 14:256–265Google Scholar
- 61.Mormone E, D’Souza S, Alexeeva V, Bederson MM, Germano IM (2014) "Footprint-free" human induced pluripotent stem cell-derived astrocytes for in vivo cell-based therapy. Stem Cells Dev. doi: 10.1089/scd.2014.0151