Neural stem cells, whether derived as above or from pluripotent stem cells as described in the next section, can be grafted into an adult brain. Once there, they show a remarkable ability to adjust their behavior to match their new location. Stem cells from the mouse hippocampus, for example, when implanted in the mouse olfactory-bulb-precursor pathway (see Figure 22–38), give rise to neurons that become correctly incorporated into the olfactory bulb. This capacity of neural stem cells and their progeny to adapt to a new environment in animals suggests applications in the treatment for diseases where neurons degenerate, and pure culture of neural stem cells (B) mixture (C) of differentiated neurons (red) and glial cells (green); cell nuclei dissociate cells and dissociate and switch to are blueculture in suspension culture as monolayer medium 3in medium 1 in medium 2 for injuries of the central nervous system. For example, might it be possible to use injected neural stem cells to replace the neurons that die in Parkinson’s disease or to repair accidents that sever the spinal cord?
Animals vary in their capacity for regeneration. At one extreme, planarian worms contain stem cells (neoblasts) that support continual turnover of all cell types, and an entire worm can be regenerated from practically any small body fragment or even from a single neoblast cell. Newts can regenerate limbs and other large body parts after amputation, but the cells remain restricted according to their origins: muscle cells in the regenerate derive from muscle, epidermis from epidermis, and so on. In mammals, regeneration is more limited. Nevertheless, it is becoming possible to go beyond the natural limits of wound healing by exploiting stem-cell biology. Thus, certain regions of the nervous system contain stem cells that support production of neurons in these sites throughout life. Neural stem cells can be obtained from these sites or from fetal brains, grown in culture, and then grafted back into other sites in the brain, where they are able to generate neurons appropriate to the new location.
When cells are transplanted from one site in the mammalian body to another or are removed from the body and maintained in culture, they remain largely faithful to their origins. Each type of specialized cell has a memory of its developmental history and seems fixed in its specialized fate. Some limited transformations can certainly occur, as we saw in our account of the connective-tissue cell family, and some stem cells can generate a variety of differentiated cell types, but the possibilities are restricted. Each type of stem cell serves for the renewal of one particular type of tissue, and the whole pattern of self-renewing and differentiated cells in the adult body is amazingly stable. What, at a fundamental molecular level, is the nature of these stable differences between cell types? Is there any way to override the cell memory mechanisms and force a switch from one state to another that is radically different?
We have already discussed these fundamental questions from a general standpoint in Chapter 7. Here we consider them more closely in the context of stem-cell biology, where there has been a recent revolution in our understanding and in our ability to manipulate states of cell differentiation. With further research, these advances would seem to have important practical consequences.
Figure 22–39 Neural stem cells. Shown are the steps leading from fetal brain tissue, via neurospheres (a), to a pure culture of neural stem cells (b). these stem cells can be kept proliferating as such indefinitely, or, through a change of medium, can be caused to differentiate (C) into neurons (red) and glial cells (green). neural stem cells with the same properties can also be derived, via a similar series of steps, from embryonic stem (eS) or induced pluripotent stem (ipS) cells (discussed later in this chapter). (micrographs from l. Conti et al., PLoS Biol. 3:1594–1606, 2005.)