Neural stem cells and glioblastoma stem cells: Redefining concepts

Stem cells (SCs) represent a distinctive population of undifferentiated cells with the extraordinary ability to self-renew and differentiate into multiple cell types. Owing to this, SCs play a crucial role in maintaining tissue homeostasis, providing a source for the replacement of cell losses due to normal wear and tear. In addition, SCs display an unquestioned therapeutic potential, which has resulted in the development of several cell therapies for the treatment of different types of diseases. However, despite their remarkable potential, the therapeutic use of SCs must still face several challenges, which include ethical, legal and technical issues. Ethical and legal concerns are mainly related to the use of SCs obtained from human embryos, while technical problems mostly arise from the difficulty of appropriately directing the differentiation of the SCs to meet the tissue´s needs and the occurrence of events such as immune rejections. In addition, the safety of SC-based therapies is also under debate. Although they may offer a useful and harmless treatment for many pathologies, including some incurable and/or life-threatening diseases, a potential risk of tumorigenicity may also exist in some cases. Accumulating evidence also implicates SCs as the origin of, at least, some types of cancer. This is the case of glioblastoma (GBM), the most prevalent glioma type in adults, whose origin has been related to postnatal neural stem cells (NSCs), mainly located in the subventricular zone (SVZ) and the dentate gyrus in the hippocampus. It has been proposed that these NSCs may give rise to glioblastoma stem cells (GSCs), which through complex interactions with the tumor microenvironment exert a crucial effect on tumor growth and development. • Cancer stem cells are initially originated from resident stem cells, although this does not exclude the possibility that non-stem cancer cells may de-differentiate into cancer stem cells. • Glioma stem cells mimic normal stem cell behavior escaping from therapies targeting dividing cells. • Multiple mechanisms are involved in the crosstalk between glioblastoma and tumor microenvironment, including local regulation and distal hormonal signals and inflammatory mediators. • Cellular heterogeneity in glioblastoma is mainly due to the existence of a unique population of cancer stem cells, which are known as glioma stem cells.