In vivo proliferation of oligodendrocyte progenitors expressing PDGF?R during early remyelination

Redwine, Jeffrey M.; Armstrong, Regina C.

doi:10.1002/(sici)1097-4695(19981115)37:3<413::aid-neu7>3.0.co;2-8

Cited by 236 publications

(245 citation statements)

References 59 publications

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“…It is possible that lowered numbers of CD4 ϩ T lymphocytes and macrophages result in decreased levels of potentially cytotoxic factors that allow for increased expression of myelinencoding genes (30,31). Alternatively, oligodendrocyte progenitor cells, which are present within the adult CNS and have been shown to participate in remyelination, may be attracted to damaged areas within the spinal cord in the absence of CXCL10 activity (32)(33)(34). Although we do not know whether myelin repair in the anti-CXCL10-treated mice is associated with functional recovery from conduction block, other studies have demonstrated that conduction velocity and frequency response properties of axons are restored to near normal values following remyelination (35).…”

Section: Discussionmentioning

confidence: 99%

Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis

Liu¹,

Keirstead

Lane³

2001

The Journal of Immunology

204

245

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Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a chronic demyelinating disease with clinical and histological similarities with the human demyelinating disease multiple sclerosis (MS). Following MHV infection, chemokines including CXC chemokine ligand (CXCL)10 (IFN inducible protein 10 kDa), CXCL9 (monokine induced by IFN-γ), and CC chemokine ligand 5 (RANTES) are expressed during both acute and chronic stages of disease suggesting a role for these molecules in disease exacerbation. Previous studies have shown that during the acute phase of infection, T lymphocytes are recruited into the CNS by the chemokines CXCL10 and CXCL9. In the present study, MHV-infected mice with established demyelination were treated with antisera against these two chemokines, and disease severity was assessed. Treatment with anti-CXCL10 reduced CD4+ T lymphocyte and macrophage invasion, diminished expression of IFN-γ and CC chemokine ligand 5, inhibited progression of demyelination, and increased remyelination. Anti-CXCL10 treatment also resulted in an impediment of clinical disease progression that was characterized by a dramatic improvement in neurological function. Treatment with antisera against CXCL9 was without effect, demonstrating a critical role for CXCL10 in inflammatory demyelination in this model. These findings document a novel therapeutic strategy using Ab-mediated neutralization of a key chemokine as a possible treatment for chronic human inflammatory demyelinating diseases such as MS.

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Section: Discussionmentioning

confidence: 99%

Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis

Liu¹,

Keirstead

Lane³

2001

The Journal of Immunology

204

245

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“…The notion that OPCs are the main remyelinating cells of the adult CNS emerged from studies showing remyelination after focal demyelination by resident progenitor cells [49,50]. Tissue OPCs expressing NG2 and platelet-derived growth factor receptor-α on their cell surface are mobilized in response to demyelination [49,[51][52][53]. Recent studies provided the definitive proof that these cells are indeed the main remyelinating cell in the CNS following a demyelinating injury [54,55].…”

Section: Adult Precursor Cells Can Generate Remyelinating Oligodendromentioning

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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“…The expression of platelet-derived growth factor α receptors (PDGFαRs) increases during the proliferation of NG2 cells, and NG2 proteoglycan expression disappears as NG2 cells differentiate into mature oligodendrocytes [46] . However, it is not the intention of this article to present a detailed review of the signaling pathways in MS.…”

Section: Remyelination In Multiple Sclerosis (Ms): Ng2 Cells Functionmentioning

confidence: 99%

Roles of NG2 glial cells in diseases of the central nervous system

Zhao

2011

Neurosci. Bull.

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In vivo proliferation of oligodendrocyte progenitors expressing PDGF?R during early remyelination

Cited by 236 publications

References 59 publications

Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis

Neutralization of the Chemokine CXCL10 Reduces Inflammatory Cell Invasion and Demyelination and Improves Neurological Function in a Viral Model of Multiple Sclerosis

Cell Therapy for Multiple Sclerosis

Roles of NG2 glial cells in diseases of the central nervous system

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