Stem cells offer the potential for regeneration of lost tissue in neurological disease, including multiple sclerosis (MS). Their development in vitro and their use in vivo in animal models of degenerative neurological disease and recent first efforts in human clinical trials were the topics of a recent international meeting sponsored by the Multiple Sclerosis International Federation and the National Multiple Sclerosis Society on "Stem Cells & MS: Prospects and Strategies" Participants reviewed the current state of knowledge about the potential use of stem and progenitor cells in MS and other degenerative neurological disorders and outlined a series of urgent fundamental and applied clinical research priorities that should allow the potential of regeneration of damaged tissue in MS to be assessed and pursued.
"T he potential for neural stem cells to produce regeneration in the central nervous system (CNS) has reawakened interest in their therapeutic potential (Louro and Pearse, 2008; Pollard and Conti, 2007; Sahni and Kessler, 2010; Sharp and Keirstead, 2009). However, translation of this potential into clinical reality is proving difficult (Duncan et al., 2008; Regenberg et al., 2009). Understanding the factors that can modulate the behavior of neural stem cells would facilitate the development of cellular-based therapies. "
[Show abstract][Hide abstract] ABSTRACT: Abstract Application of sinusoidal electric fields (EFs) has been observed to affect cellular processes, including alignment, proliferation, and differentiation. In the present study, we applied low-frequency alternating current (AC) EFs to porcine neural progenitor cells (pNPCs) and investigated the effects on cell patterning, proliferation, and differentiation. pNPCs were grown directly on interdigitated electrodes (IDEs) localizing the EFs to a region accessible visually for fluorescence-based assays. Cultures of pNPCs were exposed to EFs (1 V/cm) of 1 Hz, 10 Hz, and 50 Hz for 3, 7, and 14 days and compared to control cultures. Immunocytochemistry was performed to evaluate the expression of neural markers. pNPCs grew uniformly with no evidence of alignment to the EFs and no change in cell numbers when compared with controls. Nestin expression was shown in all groups at 3 and 7 days, but not at 14 days. NG2 expression was low in all groups. Co-expression of glial fibrillary acidic protein (GFAP) and TUJ1 was significantly higher in the cultures exposed to 10- and 50-Hz EFs than the controls. In summary, sinusoidal AC EFs via IDEs did not alter the alignment and proliferation of pNPCs, but higher frequency stimulation appeared to delay differentiation into mature astrocytes.
"Exp. of PMD as well as Batten's disease, another fatal disorder (Clinical Trials Identifier NCT01005004). Weighing the potential for cell-based therapies with life-long management or potential decreased quality of patient's lives, there is a significant responsibility for institutions to carefully consider the risks and benefits to patients with non-fatal, yet progressive, conditions such as MS, spinal cord injury and cerebral palsy (Duncan et al. 2008). "
[Show abstract][Hide abstract] ABSTRACT: Oligodendrocytes are the primary source of myelin in the adult central nervous system (CNS), and their dysfunction or loss underlies several diseases of both children and adults. Dysmyelinating and demyelinating diseases are thus attractive targets for cell-based strategies since replacement of a single presumably homogeneous cell type has the potential to restore functional levels of myelin. To understand the obstacles that cell-replacement therapy might face, we review oligodendrocyte biology and emphasize aspects of oligodendrocyte development that will need to be recapitulated by exogenously transplanted cells, including migration from the site of transplantation, axon recognition, terminal differentiation, axon wrapping, and myelin production and maintenance. We summarize studies in which different types of myelin-forming cells have been transplanted into the CNS and highlight the continuing challenges regarding the use of cell-based therapies for human white matter disorders.
"The discovery that NPC are present in the adult brain and that these cells are capable of forming neurons and glial cells has raised hopes that neurorestorative therapy for a wide variety of neurological disorders may be within reach (McDonald and Wojtowicz, 2005; Goya et al., 2007; Hsu et al., 2007; Duncan et al., 2008). One approach has been to implant the NPC or stem cells into the nervous system. "
[Show abstract][Hide abstract] ABSTRACT: There is a great need for pharmacological approaches to enhance neural progenitor cell (NPC) function particularly in neuroinflammatory diseases with failed neuroregeneration. In diseases such as multiple sclerosis and stroke, T-cell infiltration occurs in periventricular zones where NPCs are located and is associated with irreversible neuronal loss. We studied the effect of T-cell activation on NPC functions. NPC proliferation and neuronal differentiation were impaired by granzyme B (GrB) released by the T-cells. GrB mediated its effects by the activation of a Gi-protein-coupled receptor leading to decreased intracellular levels of cAMP and subsequent expression of the voltage-dependent potassium channel, Kv1.3. Importantly, blocking channel activity with margatoxin or blocking its expression reversed the inhibitory effects of GrB on NPCs. We have thus identified a novel pathway in neurogenesis. The increased expression of Kv1.3 in pathological conditions makes it a novel target for promoting neurorestoration.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2010; 30(14):5020-7. DOI:10.1523/JNEUROSCI.0311-10.2010 · 6.34 Impact Factor
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