Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain
Abstract
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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Remyelination is associated with proliferation and differentiation of oligodendrocyte precursor cells into mature oligodendrocytes.
“Importantly, however, a multitude of experimental evidence has shown that remyelination is associated with proliferation and differentiation of oligodendrocyte precursor cells into mature oligodendrocytes”
From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [25]
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Self-citation
- Authors
- Windrem, M. S., Nunes, M. C., Rashbaum, W. K., Schwartz, T. H., Goodman, R. A., McKhann, G., Roy, N. S., & Goldman, S. A.
- Affiliations
- Cornell University (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Goldman, Steven A
- Venue
- Nature Medicine
- Published
- 2003-12-21
- Volume
- 10
- Issue
- 1
- Pages
- 93-97
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2036564199
- Cited by
- 451
- References
- 2
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 19 · 2023: 6 · 2022: 11 · 2021: 23 · 2020: 16 · 2019: 16 · 2018: 13 · 2017: 24 · 2016: 18 · 2015: 20 · 2014: 26 · 2013: 24 · 2012: 26
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Update notices
- erratum (2004-02-01)
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Multiple Sclerosis Society
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (R01NS039559, R01-NS33106, R01NS033106, R01NS 39559)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- oligodendrocyte precursor cells, myelination, fetal brain, shiverer mice, A2B5, PSA-NCAM, xenotransplantation, oligodendrocyte differentiation, myelin basic protein, axonal myelination, astrocytes
- MeSH terms
- Adult, Animals, Demyelinating Diseases, Myelin Basic Protein, Fetus, Humans, Immunohistochemistry, Microscopy, Electron, Oligodendroglia, Stem Cells, Microscopy, Confocal, Mice
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