Role Of Neural Stem Cells Research Articles

Cross Talk between Notch and Growth Factor/Cytokine Signaling Pathways in Neural Stem Cells

Precise control of proliferation and differentiation of multipotent neural stem cells (NSCs) is crucial for proper development of the nervous system. Although signaling through the cell surface receptor Notch has been implicated in many aspects of neural development, its role in NSCs remains elusive. Here we examined how the Notch pathway cross talks with signaling for growth factors and cytokines in controlling the self-renewal and differentiation of NSCs. Both Notch and growth factors were required for active proliferation of NSCs, but each of these signals was sufficient and independent of the other to inhibit differentiation of neurons and glia. Moreover, Notch signals could support the clonal self-renewing growth of NSCs in the absence of growth factors. This growth factor-independent action of Notch involved the regulation of the cell cycle and cell-cell interactions. During differentiation of NSCs, Notch signals promoted the generation of astrocytes in collaboration with ciliary neurotrophic factor and growth factors. Their cooperative actions were likely through synergistic phosphorylation of signal transducer and activator of transcription 3 on tyrosine at position 705 and serine at position 727. Our data suggest that distinct intracellular signaling pathways operate downstream of Notch for the self-renewal of NSCs and stimulation of astrogenesis.

Neural Stem Cells, Neural Progenitors, and Neurotrophic Factors

Neural stem cells (NSCs) have been proposed as a promising cellular source for the treatment of diseases in nervous systems. NSCs can self-renew and generate major cell types of the mammalian central nervous system throughout adulthood. NSCs exist not only in the embryo, but also in the adult brain neurogenic region: the subventricular zone (SVZ) of the lateral ventricle. Embryonic stem (ES) cells acquire NSC identity with a default mechanism. Under the regulations of leukemia inhibitory factor (LIF) and fibroblast growth factors, the NSCs then become neural progenitors. Neurotrophic and differentiation factors that regulate gene expression for controlling neural cell fate and function determine the differentiation of neural progenitors in the developing mammalian brain. For clinical application of NSCs in neurodegenerative disorders and damaged neurons, there are several critical problems that remain to be resolved: 1) how to obtain enough NSCs from reliable sources for autologous transplantation; 2) how to regulate neural plasticity of different adult stem cells; 3) how to control differentiation of NSCs in the adult nervous system. In order to understand the mechanisms that control NSC differentiation and behavior, we review the ontogeny of NSCs and other stem cell plasticity of neuronal differentiation. The role of NSCs and their regulation by neurotrophic factors in CNS development are also reviewed.

Physical Activity-Mediated Functional Recovery after Spinal Cord Injury: Potential Roles of Neural Stem Cells

As data elucidating the complexity of spinal cord injury pathophysiology emerge, it is increasingly being recognized that successful repair will probably require a multifaceted approach that combines tactics from various biomedical disciplines, including pharmacology, cell transplantation, gene therapy and material sciences. Recently, new evidence highlighting the benefit of physical activity and rehabilitation interventions during the post-injury phase has provided novel possibilities in realizing effective repair after spinal cord injury. However, before a comprehensive therapeutic strategy that optimally utilizes the benefits of each of these disciplines can be designed, the basic mechanisms by which these various interventions act must be thoroughly explored and important synergistic and antagonistic interactions identified. In examining the mechanisms by which physical activity-based functional recovery after spinal cord injury is effected, endogenous neural stem cells, in our opinion, engender a potentially key role. Multipotent neural stem cells possess many faculties that abet recovery, including the ability to assess the local microenvironment and deliver biofactors that promote neuroplasticity and regeneration, as well as the potential to replenish damaged or eradicated cellular elements. Encouragingly, the functional recovery owing to physical activity-based therapies appears relatively robust, even when therapy is initiated in the chronic stage of spinal cord injury. In this article, we review experimental outcomes related to our hypothesis that endogenous neural stem cells mediate the functional recovery noted in spinal cord injury following physical activity-based treatments. Overall, the data advocates the incorporation of increased physical activity as a component of the multidimensional treatment of spinal cord injury and underscores the critical need to employ research-based mechanistic approaches for developing future advances in the rehabilitation of neurological injury and disorders.

Neurogenèse adulte : aspects fondamentaux et potentiels thérapeutiques

Neural stem cells have recently been found in the central nervous system of adult rodents and humans. In defined conditions, these multipotent cells can generate the three major cell types of the nervous system (neurons, oligodendrocytes and astrocytes). These findings raise questions on the functional role of neural stem cells in the adult brain, and point to the possibility of novel therapeutic approaches. We have been investigating the functional consequences of neural stem cells for the adult circuits of the olfactory system. We are currently investigating this unexpected juvenile characteristic for cognitive functions. For instance, we are exploring the potential of brain adaptation brought into play by adult neurogenesis. Our most recent studies show that neurogenesis contributes to long-term adjustment of the mature brain. Many questions remain to be answered, however. To what extent can we distinguish and compare neuronal production during embryogenesis and adulthood? How does a newborn cell migrate and find its target? How is cellular fate decided? By showing correlations between the regenerative capacities and cognitive functions of the adult brain, our results have interesting implications for the use of endogenous neuronal stem cells for brain repair in patients with neurodegenerative diseases or brain injury due to stroke or trauma.

Grafted Neural Stem Cells Shield the Host Environment from Oxidative Stress

Here, we present our preliminary data showing that neural stem cells (NSCs) can prevent the degeneration of striatal neurons when transplanted into the CNS prior to intoxication with 3-nitropropionic acid (3-NP). In the adult CNS, the number of NSCs, a major source of neural cell populations and plasticity-modulating factors, is relatively low if compared to that of the developing brain. This, together with the adult growth-inhibitory environment, limits its regenerative capacity. Our recent observation has shown that grafted NSCs may rescue/protect neurons in the chronically impaired mesostriatal system. On the basis of this study and because we were also intrigued by our recent observations regarding the rescue/protective role of NSCs in vitro, we decided to test the hypothesis that grafted NSCs can also be deposited preventively in the CNS (and perhaps join the pool of endogenous NSCs of the intact host brain) for later buffering and maintenance of homeostasis when the host is exposed to oxidative stress.