Regeneration and repair in multiple sclerosis: The view of experimental pathology

Blakemore, W. F.

doi:10.1016/j.jns.2007.03.006

Cited by 27 publications

(22 citation statements)

References 29 publications

(27 reference statements)

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“…These data demonstrated that remyelination was augmented after the engraftment of OPCs into the demyelinated corpus callosum, and also validated the maturation of OPCs into mature, functional oligodendrocytes. These observations support the work of others showing that transplantation of OPCs derived from induced pluripotent stem cells improves the recovery of the demyelinated spinal cord and optic chiasma [Blakemore, 2008;Hu and Zhan, 2009;Tirotta et al, 2010;Pouya et al, 2011].…”

Section: Discussionsupporting

confidence: 90%

Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation

Bojnordi¹,

Ghasemi²,

Akbari

2014

Cells Tissues Organs

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Bone marrow stromal cells (BMSCs) are a desirable cell source that may be useful for the treatment of neurodegenerative diseases given their capacity to differentiate into various types of cells. The current study aimed to investigate whether oligoprogenitor cell (OPC)-derived BMSCs have therapeutic benefits in an animal model of local demyelination. BMSCs were transdifferentiated into OPCs using a defined culture medium supplemented with a combination of inducers. The differentiation capacity of the BMSCs was evaluated at the end of the induction phase by assessing the expression levels of the glial-specific markers oligodendrocyte transcription factor 2 and O4 surface antigen. Local demyelination was induced in the corpus callosum of adult female rats via direct injection of lysophosphatidylcholine (LPC) followed by engraftment of BMSC-generated OPCs. The rats were divided into sham control, vehicle control, and cell-transplanted groups. The changes in the extent of demyelination and the robustness of the remyelination event were assessed using Luxol Fast Blue staining and immunohistochemical analysis 1 week after LPC injection and 2 weeks after cell transplantation. Consequently, transplantation of OPCs into the demyelinated corpus callosum model resulted in differentiation of the cells into mature oligodendrocytes that were immunopositive for myelin basic protein. Furthermore, OPC transplantation mitigated demyelination and augmented remyelination relative to controls. These findings suggest that BMSC-derived OPCs can be utilized in therapeutic approaches for the management of demyelination-associated diseases such as multiple sclerosis.

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Section: Discussionsupporting

confidence: 90%

Remyelination after Lysophosphatidyl Choline-Induced Demyelination Is Stimulated by Bone Marrow Stromal Cell-Derived Oligoprogenitor Cell Transplantation

Bojnordi¹,

Ghasemi²,

Akbari

2014

Cells Tissues Organs

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“…74,75 The results show that the increase in oligodendrogenesis is linked to increased proliferation of the NG2 ϩ OPC population and to morphologic changes specific to the T PLP mice. Although proliferation is a characteristic feature of OPC activation, 14,16,76 these cells also respond by changing their structure and level of expression of NG2. Morphologic changes have been reported to be characteristic of the OPC response to inflammation, 77 and may have been exaggerated by the abundance of activated myelin-specific T cells in the dentate gyrus in T PLP mice.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Adult Oligodendrogenesis by Myelin-Specific T Cells

Nielsen

Toft-Hansen

Lambertsen

et al. 2011

The American Journal of Pathology

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In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In contrast, T cells specific for ovalbumin did not stimulate the formation of new oligodendrocytes. In addition, infiltration of myelinspecific T cells enhanced the sprouting response of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system. T cell infiltration, demyelination, and axonal damage are central pathologic features of multiple sclerosis (MS). Whereas the primary immune attack on oligodendrocytes and myelin is effected by T cells, 1,2 remyelination occurs in acute plaques, also in the presence of T cells. 3,4 Remyelination depends on chondroitin sulfate NG2-expressing adult oligodendrocyte precursor cells (OPCs). 5,6 OPCs retain the capacity to proliferate and differentiate into myelinating oligodendrocytes in response to toxic or inflammatory demyelination 7-9 and other forms of central nervous system (CNS) injury such as ischemia, 10 spinal cord injury, 11,12 axonal lesions, 13,14 and inflammation. 15 During differentiation, OPCs downregulate NG2 as cells acquire markers of mature oligodendrocytes such as 2=,3=-cyclic nucleotide 3=-phosphodiesterase (CNP). 16 The axonal damage that occurs within and distal to the acute MS lesion can be modeled in the hippocampal dentate gyrus by transection of the perforant pathway (PP), resulting in degeneration of the PP axons and their myelin sheaths in the outer part of the molecular layer. [17][18][19] PP lesions also induce proliferation of OPCs, which results in formation of new oligodendrocytes. 14 These newly formed oligodendrocytes are presumed to myelinate the axonal sprouts that extend from other afferent fiber systems in the dentate gyrus 20,21 such as the associational/commissural afferents from the calretinergic hilar mossy cells. 20,22,23 Indeed, in stratum radiatum of the hippocampal CA3 region, lesion-induced axonal sprouting is associated with formation of more oligodendrocytes and more myelin. 24 Because remyelination ultimately fails in MS, 25 it is assumed that autoimmune demyelination reduces the capacity for myelin repair. 26,27 We investigated the effect of myelin-specific T cells on the formation of oligodendrocytes in the dentate gyrus of ...

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“…[5][6][7] This suggests that late OPC arrival could ultimately result in lesions containing OPCs whose differentiation is blocked. 8 Thus, understanding which molecules in MS lesions influence the rate and efficacy of OPC recruitment may contribute to designing therapies to enhance remyelination.…”

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confidence: 99%