Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain

  • A Corrigendum to this article was published on 01 February 2004


Both late-gestation and adult human forebrain contain large numbers of oligodendrocyte progenitor cells (OPCs). These cells may be identified by their A2B5+PSA-NCAM phenotype (positive for the early oligodendrocyte marker A2B5 and negative for the polysialylated neural cell adhesion molecule). We used dual-color fluorescence-activated cell sorting (FACS) to extract OPCs from 21- to 23-week-old fetal human forebrain, and A2B5 selection to extract these cells from adult white matter. When xenografted to the forebrains of newborn shiverer mice, fetal OPCs dispersed throughout the white matter and developed into oligodendrocytes and astrocytes. By 12 weeks, the host brains showed extensive myelin production, compaction and axonal myelination. Isolates of OPCs derived from adult human white matter also myelinated shiverer mouse brain, but much more rapidly than their fetal counterparts, achieving widespread and dense myelin basic protein (MBP) expression by 4 weeks after grafting. Adult OPCs generated oligodendrocytes more efficiently than fetal OPCs, and ensheathed more host axons per donor cell than fetal cells. Both fetal and adult OPC phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.

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Figure 1: Fetal human OPCs disperse rapidly to infiltrate the forebrain.
Figure 2: Engrafted human OPCs myelinate an extensive region of the forebrain.
Figure 3: Axonal ensheathment and myelin compaction by engrafted human OPCs.
Figure 4: Fetal and adult OPCs differed in speed and efficiency of myelinogenesis.


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This work was supported by the National Multiple Sclerosis Society and National Institutes of Health/National Institute of Neurological Diseases and Stroke grants R01NS39559 and R01NS33106. We thank B. Poulos of the Albert Einstein College of Medicine tissue bank and S. Kelly of the American Biological Resource tissue bank for assistance with tissue acquisition, and H. Okano for the gift of antiserum to human nestin.

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Correspondence to Steven A Goldman.

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S.A.G., N.S.R. and M.W. have patents and patent applications covering methods of isolating human oligodendrocyte progenitor cells, and aspects of the cells and uses thereof. These have been licensed by Cornell University of Q Therapeutics, a biotech company in which both Cornell University and S.A.G. have equity positions, and for which S.A.G. serves as a paid member of its scientific advisory board.

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Windrem, M., Nunes, M., Rashbaum, W. et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 10, 93–97 (2004). https://doi.org/10.1038/nm974

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