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The Journal of Neuroscience, September 1, 2000, 20(17):6404-6412
NG2-Positive Oligodendrocyte Progenitor Cells in Adult Human
Brain and Multiple Sclerosis Lesions
Ansi
Chang1,
Akiko
Nishiyama2,
John
Peterson1, 4,
John
Prineas3, and
Bruce D.
Trapp1, 4
1 Department of Neurosciences, The Lerner
Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio
44195, 2 Department of Physiology and Neurobiology,
University of Connecticut, Storrs, Connecticut 06269, 3 Department of Medicine, University of Sydney, Sydney,
Australia, and 4 Neurosciences Graduate Studies Program and
Department of Neurosciences, The Ohio State University, Columbus, Ohio
43210
Multiple sclerosis (MS) is characterized by multifocal loss of
myelin, oligodendrocytes, and axons. Potential MS therapies include
enhancement of remyelination by transplantation or manipulation of
endogenous oligodendrocyte progenitor cells. Characteristics of
endogenous oligodendrocyte progenitors in normal human brain and in MS
lesions have not been studied extensively. This report describes the
distribution of cells in sections from normal adult human brain and MS
lesions by using antibodies directed against NG2, an integral membrane
chondroitin sulfate proteoglycan expressed by oligodendrocyte
progenitor cells. Stellate-shaped NG2-positive cells were detected in
the white and gray matter of normal adult human brain and appeared as
abundant as, but distinct from, astrocytes, oligodendrocytes, and
microglia. Stellate-shaped or elongated NG2-positive cells also
were detected in chronic MS lesions. A subpopulation of the elongated
NG2-positive cells expressed the putative apoptotic signaling molecule
p75NTR. TUNEL-positive cells in three active, nine
chronic active, and four chronic inactive lesions, however, were
p75NTR-negative. These studies identify cells with
phenotypic markers of endogenous oligodendrocyte progenitors in the
mature human CNS and suggest that functional subpopulations of
NG2-positive cells exist in MS lesions. Endogenous oligodendrocyte
progenitor cells may represent a viable target for future therapies
intended to enhance remyelination in MS patients.
Key words:
oligodendrocyte progenitor cells; multiple sclerosis; remyelination; NG2; p75NTR; apoptosis
Copyright © 2000 Society for Neuroscience 0270-6474/00/20176404-09$05.00/0
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