Brent A. Reynolds

NEURAL STEM CELLS IN THE ADULT MAMMALIAN FOREBRAIN : A RELATIVELY QUIESCENT SUBPOPULATION OF SUBEPENDYMAL CELLS

Dissection of the subependyma from the lateral ventricle of the adult mouse forebrain is necessary and sufficient for the in vitro formation of clonally derived spheres of cells that exhibit stem cell properties such as self-maintenance and the generation of a large number of progeny comprising the major cell types found in the central nervous system. Killing the constitutively proliferating cells of the subependyma in vivo has no effect on the number of stem cells isolated in vitro and induces a complete repopulation of the subependyma in vivo by relatively quiescent stem cells found within the subependyma. Depleting the relatively quiescent cell population within the subependyma in vivo results in a corresponding decrease in spheres formed in vitro and in the final number of constitutively proliferating cells in vivo, suggesting that a relatively quiescent subependymal cell is the in vivo source of neural stem cells.

bFGF regulates the proliferative fate of unipotent (neuronal) and bipotent (neuronal/astroglial) EGF-generated CNS progenitor cells

In cultures of embryonic and adult mouse striatum, we previously demonstrated that EGF induces the proliferation of putative stem cells, which give rise to spheres of undifferentiated cells that can generate neurons and astrocytes. We report here that the spheres of undifferentiated cells contain mRNA and protein for the FGF receptor (FGFR1). Indirect immunocytochemistry demonstrated that many of the cells within the EGF-generated spheres were immunoreactive for FGFR1. Exogenous application of bFGF to the EGF-generated cells induced the proliferation of two progenitor cell types. The first, a bipotent progenitor cell, gave rise to cells with the antigenic and morphological properties of neurons and astrocytes; the other gave rise to cells with neuronal characteristics only. bFGF-generated cells with neuronal morphology exhibited electrophysiological properties indicative of immature central neurons. These results support the hypothesis that sequential actions of growth factors play a role in regulating the generation of neurons and astrocytes in the developing CNS.

Central nervous system growth and differentiation factors: Clinical horizons—Truth or dare?

Growth factors are potent and effective regulators of nerve-cell differentiation and survival. In the past year, several compelling studies have suggested that two proteins, glial derived neurotrophic factor and ciliary neurotrophic factor, may be useful in clinical approaches to treating injury or diseases of the nervous system. In addition, delivery of such factors to the central nervous system may be facilitated by a number of recently reported technologies: growth factor-antibody conjugates, polymer encapsulation and adenovirus vectors. These recent developments are part of new and innovative approaches towards brain repair.