The Changing Face of Neural Stem Cell Therapy in Neurologic Diseases

Einstein, Ofira; Ben‐Hur, Tamir

doi:10.1001/archneur.65.4.452

Cited by 135 publications

(92 citation statements)

References 31 publications

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“…In a Parkinson's disease model, transplanted NPCs rescued endogenous dopaminergic neurons of the mesostriatal system [156], and in models of amyotrophic lateral sclerosis transplanted NPCs prevented motor neurons from dying [157][158][159]. Transplantation experiments in models of spinal cord injury have provided several insights to the basic biological mechanisms by which the various types of precursor cells exhibit their therapeutic functions (for more detail see Einstein and Ben-Hur [160]). First, neural and mesenchymal stem and progenitor cells reduce the acute deleterious inflammatory process and induce a permissive environment for axonal regeneration after spinal cord injury [161].…”

Section: Trophic Support By Transplanted Precursor Cellsmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.

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Section: Trophic Support By Transplanted Precursor Cellsmentioning

confidence: 99%

Cell Therapy for Multiple Sclerosis

Ben‐Hur

2011

Neurotherapeutics

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“…While neural precursor cells (NPCs) have promising remyelinating potential , recent studies have suggested that they may also exert neurotrophic properties (Teng et al, 2002;Zhang et al, 2007;Einstein and Ben-Hur, 2008). We therefore hypothesized that NPC transplantation may enhance the myelin regeneration capabilities of host brain cells.…”

Section: Introductionmentioning

confidence: 99%

Transplanted Neural Precursors Enhance Host Brain-Derived Myelin Regeneration

Einstein¹,

Friedman-Levi²,

Grigoriadis³

et al. 2009

J. Neurosci.

112

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In multiple sclerosis lesions resident oligodendrocyte progenitor cells (OPCs) are present, but fail to remyelinate. In the current study we examined whether neural precursor cell (NPC) transplantation can facilitate host brain-derived remyelination. We used the chronic cuprizone-induced demyelination model in aged mice, in which slow remyelination follows cuprizone removal. NPCs were transplanted to the lateral ventricles (intracerebroventricular) of cuprizone-induced demyelinated brains. In this experimental setup, transplanted cells remained mostly in the periventricular area in an undifferentiated state. The extent of demyelination, remyelination, and proliferation of host brain regenerative cell population were examined at 1 week posttransplantation in the splenium of the corpus callosum, which was devoid of any transplanted cells. Transplantation of NPCs, but not of control, human embryonic kidney cells, significantly enhanced remyelination compared with sham-operated mice. Remyelination was performed exclusively by host brain OPCs. The proregenerative effect of transplanted NPCs was related to an increase in the proliferation of host brain OPCs. To examine the mechanism that underlies the proregenerative effect of NPCs in vitro, we used an NPC-OPC coculture system. These experiments indicated that NPCs induced the proliferation of OPCs and facilitated their differentiation into mature oligodendrocytes. The mitogenic effect of NPCs was mediated by platelet-derived growth factor-AA and fibroblast growth factor-2. In conclusion, NPC transplantation enhances hostderived myelin regeneration following chronic demyelination. This trophic effect may stimulate resident OPCs to overcome the remyelination failure in multiple sclerosis.

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“…NSCs can function as a cell source for 'restorative cell therapeutics' in sites of neuropathology (given their capacity for self-renewal and multipotentiality) [1,2]. They create an environment permissive for repair by releasing pro-regenerative and immunosuppressive proteins, and these cells have rapidly progressed to clinical trials for several neurological disorders [3][4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

Fernandes

Chari

2016

Journal of Controlled Release

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Please cite this article as: Alinda R. Fernandes, Divya M. Chari, Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy, Journal of Controlled Release (2016Release ( ), doi: 10.1016Release ( /j.jconrel.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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The Changing Face of Neural Stem Cell Therapy in Neurologic Diseases

Cited by 135 publications

References 31 publications

Cell Therapy for Multiple Sclerosis

Cell Therapy for Multiple Sclerosis

Transplanted Neural Precursors Enhance Host Brain-Derived Myelin Regeneration

Part I: Minicircle vector technology limits DNA size restrictions on ex vivo gene delivery using nanoparticle vectors: Overcoming a translational barrier in neural stem cell therapy

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