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Stem cell technology for basic science and clinical applications.

In the adult mammalian central nervous system (CNS), most of the mechanisms responsible for cell proliferation and migration are shut off; thus, the capacities for self-repair and cellular replacement are greatly diminished. Observations that cell division continues in some regions of the adult brain and some resulting cells become neurons prompted attempts to identify the progenitor cells responsible for both embryonic and postnatal neural developments. The term stem cells refers to a population of cells that is capable of extended self-renewal and the ability to generate multilineage (neurons and glia) cell types (Figure). The growing interest in the isolation and propagation of stem cells and studying stem cell biology is driven by 2 goals. The first goal is to establish an in vitro system to ellucidate the fate pathways of individual neural progenitors. Such a system can be used to determine signaling molecules controlling the generation of specific neural cell lineages and to dissect cellular mechanisms underlying the progressive processes of commitment, fate determination, and differentiation during neural development. The second goal is to use such cultured, well-characterized cells for therapeutic applications in the treatment of neurologic and neurodegenerative diseases. In many neurologic diseases, specific neural cell types or circuits degenerate. These losses may be due to genetic abnormalities of the diseased cell or may be due to the absence of enzymes, neurotransmitters, trophic factors or cofactors, or the presence of toxic substances or physical injury. Treatment of CNS disease or injury could focus on one or more steps leading to cell loss. Clinical trials show that neuron replacement for neurodegenerative diseases, such as Parkinson and Huntington diseases is feasible. Grafts of freshly dissected fetal substantia nigra have shown promising longterm clinical improvement in some patients with Parkinson disease. The improvements wereassociatedwiththesurvivalofthegrafts and dopaminergic reinnervation of the striatum. 1 Reports 2 of fetal striatal transplantation in patients with mild to severe Huntington disease suggest that neurotranplantation may improve some of the cognitive symptoms associated with the disease and may modify the course of the disease. Ex vivo gene therapy is an alternative approach that has been used in various ex