Neural stem cells: Isolation and self-renewal

The human brain is composed of more than 100 billion neurons and more than 10 times that many glia, and in spite of having a wide variety of functions and morphology depending on the individual site, they function superbly as a single community. Neural stem cells (NSCs) can be described as the source of this wide variety of cells. Stem cells are generally defined as cells that fulfill four conditions (1). They are capable of (1) proliferation, (2) self-renewal, (3) multipotency, and (4) tissue-repair ability (discussed subsequently), and NSCs are likely to fulfill those conditions. In mice, NSCs are known to be maintained by self-renewal from the time they first appear around embryo, day 8.5, until adulthood. A lineage relationship between embryonic and adult NSCs, however, has not been demonstrated. Experiments have shown that it is possible to selectively culture NSCs in the presence of growth factors by monolayer culture on an adhesive substrate (2) and by suspension culture (3), which is called the “neurosphere method” (Fig. 1). As they differentiate into the neurons, astrocytes, and oligodendrocytes that comprise the central nervous system (CNS) when the growth factors are removed, they can be said to possess multipotency. In adult mammalian brains in vivo, NSCs or NSC-like cells have been shown to be involved in neurogenesis under physiological conditions at particular sites, that is, such as the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal formation (4–6). Furthermore, recent reports have suggested that NSCs also have the ability to partly repair the damaged CNS (7,8).