The Stem Cells as a Potential Treatment for Neurodegeneration

Cell degeneration and death, be it extensive and widespread, such as in metabolic disorders, or focal and selective as in Parkinson’s disease (PD), is the underlying feature of many neurological diseases. Thus, the replacement of cells lost by injury or disease has become a central tenet in strategies aiming at the development of novel therapeutic approaches for neurodegenerative disorders. In addition to the in vivo recruitment of endogenous cells, which is now emerging as a promising novel strategy, the transplantation of new, exogenously generated brain cells is probably the most extensively studied methodology for cell replacement in the central nervous system, with the initial experimental clinical studies in PD dating back to the early 1970s (Bjorklund, A. and Stenevi, U., 1984, Intracerebral neural implants: neuronal replacement and reconstruction of damaged circuitries. Annu Rev Neurosci 7 , 279–308; Snyder, B. J. and Olanow, C. W., 2005, Stem cell treatment for Parkinson’s disease: an update for 2005. Curr Opin Neurol 18 , 376–85). The need to generate the cells to be transplanted in large quantities and in a reproducible, steady, and safe fashion has long represented one of the major issues in this field, regardless of whether one was trying to produce specific cell subtypes or uncommitted and highly plastic neural precursors, which would respond to local, instructive cues, upon transplantation into the damaged area. Neural stem cells (NSCs), with their capacity for long-term expansion in vitro and their extensive functional stability and plasticity, allow now for the establishment of cultures of mature neural cells as well as highly undifferentiated precursors and are emerging as one of the most amenable cell sources for neural transplantation (Gage, F. H., 2000 , Mammalian neural stem cells. Science 287 , 1433–8; McKay, R., 1997 , Stem cells in the central nervous system. Science 276 , 66–71). This chapter illustrates the basic aspect of the handling and preparation of NSCs for experimental transplantation in two animal models of neurodegenerative disorders, namely, postcontusion spinal cord injury and multiple sclerosis.