Functional Capacities of Transplanted Cell-Sorted Adult Oligodendrocytes

Duncan, Ian D.; Paı́no, Carlos Luis; Archer, David; Wood, Patrick M.

doi:10.1159/000111655

Cited by 100 publications

(22 citation statements)

References 18 publications

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“…Multiple approaches have been developed for OPC purification; each has its own merits. Compared to other OPC isolation methods such as costly immunopanning 5,9,10 and technically demanding differential gradient centrifugation 7,8,12 , the method for OPC preparation through oligosphere generation from both mouse and rat neural progenitor cells is simple and straightforward 20,21,26 . It can be easily followed by a researcher without prior OPC isolation experience.…”

Section: Anticipated Resultsmentioning

confidence: 99%

“…These include proliferating OPCs, characterized by expression of progenitor cell markers such as the platelet-derived growth factor alpha receptor (PDGFaR) with a bipolar or tripoIar morphology, intermediate immature oligodendrocytes, expressing markers recognized by the O4 antibody with a multipolar morphology, and finally mature myelinating oligodendrocytes, expressing myelinspecific proteins such as myelin basic protein. When transplanted into the brain of hypomyelinated hosts, oligodendrocyte precursors can migrate a significant distance, and give rise to a large number of mature oligodendrocytes 6,7 , as well as myelinate axons 8 . Simple methods for the isolation and purification of workable quantities of OPCs not only aid in efforts to better understand oligodendrocyte development, function and axonoligodendroglial interactions but also provide an indispensable tool for myelin repair research.…”

Section: Introductionmentioning

confidence: 99%

“…Simple methods for the isolation and purification of workable quantities of OPCs not only aid in efforts to better understand oligodendrocyte development, function and axonoligodendroglial interactions but also provide an indispensable tool for myelin repair research. Several methods for isolation of rat OPCs from the CNS have been described, such as immunopanning 5,9,10 , fluorescence-activated cell sorting (FACS) by exploiting cell surface-specific antigens 5,11 , differential gradient centrifugation 7,8,12 or a shaking method based on differential adherent properties of glia 13,14 , which permits the separation of rat OPCs from the astroglial cells in the mixed glial culture by shearing forces.…”

Section: Introductionmentioning

confidence: 99%

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Isolation and culture of rat and mouse oligodendrocyte precursor cells

et al. 2007

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Section: Anticipated Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Isolation and culture of rat and mouse oligodendrocyte precursor cells

et al. 2007

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“…The ability of transplanted glial cells to ensheath axons and synthesize myelin when transplanted into dysmyelinating mutants or chemically created models of demyelination has been studied extensively (1)(2)(3)(4)(5)(6). Until now the primary assay of myelin-forming grafts has of necessity been anatomical rather than functional or electrophysiological.…”

mentioning

confidence: 99%

Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat.

Utzschneider

Archer²,

Kocsis³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

134

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A central issue in transplantation research is to determine how and when transplantation of neural tissue can influence the development and function of the mammalian central nervous system. Of particular interest is whether electrophysiological function in the traumatized or diseased mammalian central nervous system can be improved by the replacement of cellular elements that are missing or damaged. Although it is known that transplantation of neural tissue can lead to functional improvement in models of neurological disease characterized by neuronal loss, less is known about results of transplantation in disorders of myelin. We report here that transplantation of glial cells into the dorsal columns of neonatal myelin-deflcient rat spinal cords leads to myelination and a 3-fold increase in conduction velocity. We also show that impulses can propagate into and out of the transplant region and that axons myelinated by transplanted cells do not have impaired frequency-response properties. These results demonstrate that myelination following central nervous system glial cell transplantation enhances action potential conduction in myelin-deficient axons, with conduction velocity approaching normal values.The ability of transplanted glial cells to ensheath axons and synthesize myelin when transplanted into dysmyelinating mutants or chemically created models of demyelination has been studied extensively (1-6). Until now the primary assay of myelin-forming grafts has of necessity been anatomical rather than functional or electrophysiological. However, the formation of myelin by transplanted cells does not in itself ensure secure impulse conduction. Impulse conduction after glial cell transplantation depends not only on myelination but on deployment of adequate numbers and types of ion channels at the newly formed nodes of Ranvier (7-9). Moreover, incomplete or patchy remyelination might be expected to lead to conduction failure due to impedance mismatch, which occurs at junctions between myelinated and nonmyelinated axon regions (10, 11); similarly, failure to form mature paranodal axoglial junctions can shunt action current and interfere with conduction (12, 13). In the present experiments, we transplanted central nervous system (CNS) myelin-forming cells into the spinal cord of the myelin-deficient (md) rat, a mutant that lacks CNS myelin, and studied conduction properties of the axons in the region of transplantation. The absence of host myelin in this system permits positive confirmation that functional changes seen after transplantation are due to the transplanted cells and not to background host myelination (2, 3). Electrophysiological studies from the md rat spinal cord have shown that while the amyelinated fibers ofthe md rat are capable of secure impulse conduction, they do so at -1/4 the conduction velocity of age-matched controls (14). We report here that myelination ofThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "adve...

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“…Although some studies have suggested that mature differentiated oligodendrocytes are useful myelinating cells, 10 the majority view is that mitotic 65 and migratory 14,66,67 capacities are vital prerequisites for successful remyelination, and that postmitotic oligodendrocytes, lacking these competencies, do not readily recapitulate their development to form myelin sheaths again. 14,68,69 Despite their motility, oligodendrocyte progenitors show poor survival and migration when implanted into normal white matter, although they are able to populate and remyelinate when injected into, or very close to, lesioned tissue.…”

Section: Choice Of Reparative Cellmentioning

confidence: 99%

Cell therapy in demyelinating diseases

2004

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Summary:Multiple sclerosis presents particular and serious problems to those attempting to develop cell-based therapies: the occurrence of innumerable lesions scattered throughout the CNS, axon loss, astrocytosis, and a continuing inflammatory process, to name but a few. Nevertheless, the limited and relatively focused nature of damage to oligodendrocytes and myelin, at least in early disease, the large body of available knowledge concerning the biology of oligodendrocytes, and the success of experimental myelin repair, have allowed cautious optimism that therapies may be possible. Here, we review the clinical and biological problems presented by multiple sclerosis in the context of cell therapies, and the neuroscientific background to the development of strategies for myelin repair. We attempt to highlight those areas where difficulties have yet to be resolved and draw on a variety of more recent experimental findings to speculate on how remyelinating therapies are likely to develop in the foreseeable future.

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Functional Capacities of Transplanted Cell-Sorted Adult Oligodendrocytes

Cited by 100 publications

References 18 publications

Isolation and culture of rat and mouse oligodendrocyte precursor cells

Isolation and culture of rat and mouse oligodendrocyte precursor cells

Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat.

Cell therapy in demyelinating diseases

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