Establishment and properties of neural stem cell clones: Plasticity in vitro and in vivo

The study of the basic physiology of the neural precursors generated during brain development is driven by two inextricably linked goals. First, such knowledge is instrumental to our understanding of how the high degree of ce llular complexity of the mature central nervous system (CNS) is generated, and how to dissect the steps of proliferation, fate commitment, and differe ntiation that lead early pluripotent neural progenitors to give rise to mat ure CNS cells. Second, it is hoped that the isolation, propagation, and man ipulation of brain precursors and, particularly, of multipotent neural stem cells (NSCs), will lead to therapeutic applications in neurological disord ers,The debate is still open concerning the most appropriate definition of a stem cell and on how it is best identified, characterized, and manipulate d. By adopting an operational definition of NSCs, we review some of the bas ic findings in this area and elaborate on their potential threapeutic appli cations, Further, we discuss recent evidence from our two groups that descr ibe, based on that rigorous definition, the isolation and propagation of cl ones of NSCs from the human fetal brain and illustrate how they have begun to show promise for neural cell replacement and molecular support therapy i n models of degenerative CNS diseases,The extensive propagation and engraft ment potential of human CNS stem cells may, in the not-too-distant-future, be directed towards genuine clinical therapeutic ends, and may open novel a nd multifaceted strategies for redressing a variety of heretofore untreatab le CNS dysfunctions.