Figure 1. Neural stem cells form the nervous system and are present throughout development. Following fertilization of an egg with sperm, a blastocyst forms that contains a group of cells called the inner cell mass (ICM). Cells from the ICM are totipotent (i.e. they can form any tissue in the body). When grown in culture, ICM cells are called embryonic stem (ES) cells. Later during embryogenesis, the neural tube contains multipotent neuroepithelial cells that can differentiate into neurons, astrocytes and oligodendrocytes. These cells can be grown in adherent culture as neuroepithelial (NEP) cells, or floating in suspension as neurospheres. In the adult brain, neural stem and progenitor cells are localized to the subventricular zone (SVZ) surrounding the anterior lateral ventricles and the subgranular layer (SGL) of the dentate gyrus of the hippocampus. Cells from the SVZ migrate along the rostral migratory stream to the olfactory bulb, where they differentiate into olfactory neurons. Cells from the SGL migrate into the granule cell layer of the hippocampus and differentiate into granule neurons. Neural stem cells are also found in scattered regions throughout the adult brain, albeit in lower numbers. Adult NSCs are usually grown floating in suspension as neurospheres. Current evidence suggests there is more than one kind of neurosphere that can be isolated from the adult brain.

Figure 2. Transplantation of exogenous cells is one route for neural stem cell therapy. In the nervous system, the best results are obtained when cells are derived from cells that are already committed to a neural lineage (if derived from ES cells) or from the same brain region to which they will be transplanted (NSCs). Once isolated, cells can be expanded in culture using growth factors. Specific subpopulations of cells (e.g. NSCs, NRPs or GRPs) can be selected from these cultures, and expanded again, if necessary.

Figure 3. Mobilization of neural stem cells is most likely in areas that undergo neurogenesis in the adult brain. In the adult hippocampus, NSCs are located in the subgranular layer (SGL) of the dentate gyrus (DG). Following division of neural stem and/or precursor cells (green circles), newborn cells migrate into the granule cell layer that makes up the DG. Factors that promote neurogenesis include exercise, diet, hormones and growth factors.

Figure 4. Delivery of growth factors into the adult brain is similar to the protocol for transplantation of cells into the adult brain. In this case, neural stem or progenitor cells are genetically engineered to secrete protective growth factors, such as BDNF or GDNF. Following expansion in culture to increase the number of available cells, the engineered cells are transplanted into the adult brain, where they secrete protective growth factors into their environment.