Concise Review: Self-renewal in the Central Nervous System: Neural Stem Cells from Embryo to Adult

The recent discovery of neural stem cells (NSCs) in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate future therapeutic approaches for the cure of neurodegenerative diseases. These studies are finally at the clinical stage, and some of them are already under way. The definition of a bona fide stem cell has long been the object of much debate focused on the establishment of standard and univocal criteria to distinguish between stem and progenitor cells. It is commonly accepted that NSCs have to fulfill two basic requirements, the capacity for long-term self-renewal and the potential for differentiation, which account for their physiological role, namely central nervous system tissue homeostasis. Strategies such as immortalization or reprogramming of somatic cells to the embryonic-like stage of pluripotency indicate the relevance of extensive self-renewal ability of NSCs either in vitro or in vivo. Moreover, the discovery of stem-like tumor cells in brain tumors, such as gliomas, accompanied by the isolation of these cells through the same paradigm used for related healthy cells, has provided further evidence of the key role that self-renewal plays in the development and progression of neurodegenerative diseases and cancer. In this review we provide an overview of the current understanding of the self-renewal capacity of nontransformed human NSCs, with or without immortalization or reprogramming, and of stem-like tumor cells, referring to both research and therapeutic studies.