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Zhang, Su‐Chun; Lundberg, Cathryn; Lipsitz, David; O'Connor, Lawrence T.; Duncan, Ian D.

doi:10.1023/a:1006953023845

Cited by 103 publications

(31 citation statements)

References 48 publications

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“…The neural precursor cells in suspension culture (''neurospheres'') were prepared from subependymal striata of Wistar rats aged 3 and 16 months according to a protocol detailed previously (13,15). The culture medium was DMEM͞F-12 (1:1) supplemented with insulin (25 g͞ml), transferrin (100 g͞ml), progesterone (20 nM), putrescine (60 M), and sodium selenite (30 nM).…”

Section: Methodsmentioning

confidence: 99%

“…The outgrowth of the sphere was examined under the phase-contrast microscope, and the images were photographed and stored in a computer. The longest distance from the edge of a sphere to the cell body in each quarter of the outgrowth was measured and the average distance of cells moved out of a single sphere at specific time points was calculated (13). At least 8 spheres were followed throughout the period of each individual experiment, and the experiment was repeated twice.…”

Section: Methodsmentioning

confidence: 99%

“…Free-floating spheres or coverslip cultures were immunolabeled with fluorescein-tagged secondary antibodies (Jackson ImmunoResearch) according to the procedure detailed previously (13). The following primary antibodies were used.…”

Section: Methodsmentioning

confidence: 99%

“…We have been studying the transition from multipotent precursor cells to lineage-restricted OPs and have shown that it is possible to generate a large number of self-renewing OPs from neural precursor cells derived from embryonic and neonatal brain (13,14). Because multipotent stem cells exist in adult CNS, we sought to explore whether the OPs derived from adult neural stem or precursor cells have the capacity for extensive myelination.…”

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confidence: 99%

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Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

Zhang

Duncan

1999

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

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189

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Remyelination of focal areas of the central nervous system (CNS) in animals can be achieved by transplantation of glial cells, yet the source of these cells in humans to similarly treat myelin disorders is limited at present to fetal tissue. Multipotent precursor cells are present in the CNS of adult as well as embryonic and neonatal animals and can differentiate into lineage-restricted progenitors such as oligodendroglial progenitors (OPs). The OPs present in adults have a different phenotype from those seen in earlier life, and their potential role in CNS repair remains unknown. To gain insights into the potential to manipulate the myelinating capacity of these precursor and͞or progenitor cells, we generated a homogenous culture of OPs from neural precursor cells isolated from adult rat subependymal tissues. Phenotypic characterization indicated that these OPs resembled neonatal rather than adult OPs and produced robust myelin after transplantation. The ability to generate such cells from the adult brain therefore opens an avenue to explore the potential of these cells for repairing myelin disorders in adulthood.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

Zhang

Duncan

1999

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

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189

106

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“…After MR imaging, the (fixed) spinal cord specimens were cryoprotected and cut at 12-m slice thickness. Sequential sections were stained for iron by using the Prussian blue reaction, for myelin by using antiproteolipid protein antibody, for astrocytes by using anti-glial fibrillary acidic protein antibody, and for microglia by using isolectin B4 as described (20,21).…”

Section: Mr Imaging and Histopathological Correlationmentioning

confidence: 99%

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination

Bulte

Zhang

Gelderen

et al. 1999

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

517

334

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Demyelination is a common pathological finding in human neurological diseases and frequently persists as a result of failure of endogenous repair. Transplanted oligodendrocytes and their precursor cells can (re)myelinate axons, raising the possibility of therapeutic intervention. The migratory capacity of transplanted cells is of key importance in determining the extent of (re)myelination and can, at present, be evaluated only by using invasive and irreversible procedures. We have exploited the transferrin receptor as an efficient intracellular delivery device for magnetic nanoparticles, and transplanted tagged oligodendrocyte progenitor cells into the spinal cord of myelin-deficient rats. Cell migration could be easily detected by using three-dimensional magnetic resonance microscopy, with a close correlation between the areas of contrast enhancement and the achieved extent of myelination. The present results demonstrate that magnetic resonance tracking of transplanted oligodendrocyte progenitors is feasible; this technique has the potential to be easily extended to other neurotransplantation studies involving different precursor cell types. Demyelination is an important pathological component of multiple sclerosis and other neurological disorders. Recent research has suggested that it is possible to promote (re)myelination in animal models of abnormal myelination or demyelination (1-3), either by endogenous oligodendrocytes or exogenous myelinating cells. The latter repair mechanism has received particular attention, because it has been shown that transplanted oligodendrocyte precursor cells can myelinate large areas in the central nervous system (4). A similar therapeutic approach in humans may be pursued and is supported by the safety and effectiveness of human neurotransplantation studies (5, 6). The clinical outcome of such studies will be directly determined by the extent of myelination, and thus by the immediate dispersion, migratory capacity, and long-term survival of grafted cells. A technique that could monitor the grafted cell migration continuously and noninvasively is crucial to guide further advances in neurotransplantation research. We hypothesized that tagging grafted cells with a magnetic label might allow magnetic resonance (MR) tracking of their migratory capacity, not unlike an earlier MR microscopy study that used labeled progeny cells to follow cell movements and lineages in the developing embryo (7). Magnetically labeled cells previously have received interest to study neural grafting procedures (8, 9) and cellular trafficking (10-13) by MR imaging.Oligodendrocyte progenitors have a greater migratory and myelinating capacity than mature glial cells (14, 15). We therefore chose the rat oligodendrocyte progenitor cell line 17) as the graft, with the myelin-deficient (md) rat as a recipient, because the migration pattern of LacZ ϩ CG-4 cells has been documented in detail with this model (18). The md rat carries an X-linked recessive mutation in the proteolipid protein gene and is characteriz...

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Fractionation and enrichment of oligodendrocytes from developing human brain

et al. 1999

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Enriched cultures of human oligodendrocytes were obtained from fetal brain specimens between 16 and 21 gestational weeks. Brain cells were separated over a Percoll density gradient and collected as two fractions with initial relative densities of approximately 1.035 g/ml and 1.102 g/ml, for fractions 1 and 2, respectively. After separation, 58.3 and 67.7% of the cells in fractions 1 and 2, respectively, were labeled by the antibody O4 that recognizes immature oligodendrocytes. A total of 15.5 and 29.4% of the cells in fractions 1 and 2, respectively, were positive for tubulin-beta(III), a marker for neurons but none of the freshly isolated cells were positive for glial fibrillary acidic protein (GFAP), a protein associated with astrocytes in the central nervous system. When the fractionated cells were cultured on poly-ornithine coated coverslips for 3 days and processed for immunocytochemistry, the percentage of O4+ oligodendrocytes decreased to less than 4% whereas GFAP+ cells increased to 1.8 and 12.4% for fractions 1 and 2 respectively. The percentage of tubulin-betaIII+ cells increased to 46 and 61% in cultures from the two Percoll fractions. This increase is probably due to the decrease in the number of oligodendrocytes. To avoid the loss of oligodendrocytes, cells were cultured as free-floating aggregates in the presence of 20 ng/ml of fibroblast growth factor-2 for 2 weeks. The resultant cultures became enriched for oligodendrocytes as demonstrated by cellular morphology and by positive O4 labeling. The method described here provides a means of obtaining enriched cultures of immature human oligodendrocytes for developmental and transplantation studies.

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Cited by 103 publications

References 48 publications

Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity

Neurotransplantation of magnetically labeled oligodendrocyte progenitors: Magnetic resonance tracking of cell migration and myelination

Fractionation and enrichment of oligodendrocytes from developing human brain

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