Adherent Self-Renewable Human Embryonic Stem Cell-Derived Neural Stem Cell Line: Functional Engraftment in Experimental Stroke Model

Department of Neurosurgery and Stanford Stroke Center, Stanford University School of Medicine, Stanford, California, USA.
PLoS ONE (Impact Factor: 3.23). 02/2008; 3(2):e1644. DOI: 10.1371/journal.pone.0001644
Source: PubMed

ABSTRACT

Human embryonic stem cells (hESCs) offer a virtually unlimited source of neural cells for structural repair in neurological disorders, such as stroke. Neural cells can be derived from hESCs either by direct enrichment, or by isolating specific growth factor-responsive and expandable populations of human neural stem cells (hNSCs). Studies have indicated that the direct enrichment method generates a heterogeneous population of cells that may contain residual undifferentiated stem cells that could lead to tumor formation in vivo.

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Available from: Anne-Lise D D'Angelo
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    • "However, their identity as true radial glial cells that recapitulate their in vivo counterparts is debatable. Notwithstanding the phenotypic consistency of SENAs, an isolated human neural stem cell line termed SD56, expressing vimentin, nestin and 3CB2 (markers of early appearing radial glia (Prada et al., 1995)) showed extensive migration without tumorigenesis around a striatal ischaemic lesion in the rat, significantly improving the independent use of the stroke impaired forelimb (Daadi et al., 2008). Perhaps a more accurate paradigm of radial glial cell transplantation is the C6 glioma derived radial glia-like cell line C6- R. C6-R cells show a bipolar morphology in vitro and support neuronal migration, while expressing markers typical of in vivo radial glia including vimentin, nestin, glial fibrillary acidic protein (GFAP) and RC1 (Friedlander et al., 1998). "

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    • "Culturing condition might reduce tumorigenesis risk of transplanted ESC-derived neural cells. For example, neural cells derived from human ESCs under defined inductive culturing condition (named SD56) did not show chromosome abnormalities after differentiation and tumor formation after implantation into ischemic rat brains and naive nude rat brains and flanks [19]. Malignant transformation of ESC-derived neural cells has been demonstrated to be related to postischemic environment probably by the stimulation of various local cytokine [26]. "
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    ABSTRACT: In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs), inducible pluripotent stem cells (iPSCs), neural stem cells (NSCs), and mesenchymal stem cell (MSCs) might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.
    Full-text · Article · Feb 2014
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    • "ESC studies in animal stroke models have been concerned with mechanistic aspects rather than functional efficacy, and report only isolation, neutralization,89 and the electrophysiological activity of differentiated neuronal cells.90 Undifferentiated ESCs grafted into rat brains have differentiated and integrated with host tissues in stroke models,91 showing improved functional outcomes on the cylinder test, which measures the spontaneous use of forelimbs.92 "
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    ABSTRACT: Stroke affects one in every six people worldwide, and is the leading cause of adult disability. Some spontaneous recovery is usual but of limited extent, and the mechanisms of late recovery are not completely understood. Endogenous neurogenesis in humans is thought to contribute to repair, but its extent is unknown. Exogenous cell therapy is promising as a means of augmenting brain repair, with evidence in animal stroke models of cell migration, survival, and differentiation, enhanced endogenous angiogenesis and neurogenesis, immunomodulation, and the secretion of trophic factors by stem cells from a variety of sources, but the potential mechanisms of action are incompletely understood. In the animal models of stroke, both mesenchymal stem cells (MSCs) and neural stem cells (NSCs) improve functional recovery, and MSCs reduce the infarct volume when administered acutely, but the heterogeneity in the choice of assessment scales, publication bias, and the possible confounding effects of immunosuppressants make the comparison of effects across cell types difficult. The use of adult-derived cells avoids the ethical issues around embryonic cells but may have more restricted differentiation potential. The use of autologous cells avoids rejection risk, but the sources are restricted, and culture expansion may be necessary, delaying treatment. Allogeneic cells offer controlled cell numbers and immediate availability, which may have advantages for acute treatment. Early clinical trials of both NSCs and MSCs are ongoing, and clinical safety data are emerging from limited numbers of selected patients. Ongoing research to identify prognostic imaging markers may help to improve patient selection, and the novel imaging techniques may identify biomarkers of recovery and the mechanism of action for cell therapies.
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