Article

Progenitor cell-based myelination as a model for cell-based therapy of the central nervous system.

Department of Neurology, University of Rochester Medical Center, NY 14642, USA.
Ernst Schering Research Foundation workshop 02/2006; pp.195-213
Source: PubMed

ABSTRACT Diseases of the brain and spinal cord are especially daunting challenges for cell-based strategies of repair, given the multiplicity of cell types within the adult central nervous system, and the precision with which they must interact in both space and time. Nonetheless, a number of diseases are especially appropriate for cell-based therapy, in particular those in which single phenotypes are lost. Foremost among these are the disorders of myelin, in which oligodendrocytes are the specific and often sole victims of the underlying disease process. These include not only the vascular, traumatic, and inflammatory demyelinations of adulthood, but also the congenital and childhood dysmyelinating syndromes of the pediatric leukodystrophies. These congenital disorders of myelin formation and maintenance may present especially compelling targets for cell-based neurological therapy.

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    Article: Derivation of glial restricted precursors from E13 mice.
    André W Phillips, Sina Falahati, Roshi DeSilva, Irina Shats, Joel Marx, Edwin Arauz, Douglas A Kerr, Jeffrey D Rothstein, Michael V Johnston, Ali Fatemi
    [show abstract] [hide abstract]
    ABSTRACT: This is a protocol for derivation of glial restricted precursor (GRP) cells from the spinal cord of E13 mouse fetuses. These cells are early precursors within the oligodendrocytic cell lineage. Recently, these cells have been studied as potential source for restorative therapies in white matter diseases. Periventricular leukomalacia (PVL) is the leading cause of non-genetic white matter disease in childhood and affects up to 50% of extremely premature infants. The data suggest a heightened susceptibility of the developing brain to hypoxia-ischemia, oxidative stress and excitotoxicity that selectively targets nascent white matter. Glial restricted precursors (GRP), oligodendrocyte progenitor cells (OPC) and immature oligodendrocytes (preOL) seem to be key players in the development of PVL and are the subject of continuing studies. Furthermore, previous studies have identified a subset of CNS tissue that has increased susceptibility to glutamate excitotoxicity as well as a developmental pattern to this susceptibility. Our laboratory is currently investigating the role of oligodendrocyte progenitors in PVL and use cells at the GRP stage of development. We utilize these derived GRP cells in several experimental paradigms to test their response to select stresses consistent with PVL. GRP cells can be manipulated in vitro into OPCs and preOL for transplantation experiments with mouse PVL models and in vitro models of PVL-like insults including hypoxia-ischemia. By using cultured cells and in vitro studies there would be reduced variability between experiments which facilitates interpretation of the data. Cultured cells also allows for enrichment of the GRP population while minimizing the impact of contaminating cells of non-GRP phenotype.
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Keywords

adult central nervous system
 
cell types
 
cell-based neurological therapy
 
cell-based strategies
 
cell-based therapy
 
childhood dysmyelinating syndromes
 
congenital
 
congenital disorders
 
diseases
 
inflammatory demyelinations
 
sole victims
 
spinal cord
 
underlying disease process
 
vascular