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

Martha S. Windrem, Marta C. Nunes, William K. Rashbaum, Theodore H. Schwartz, Robert A. Goodman, Guy McKhann, Neeta Roy, Steven A. Goldman

Research output: Contribution to journalArticle

307 Citations (Scopus)

Abstract

Both late-gestation and adult human forebrain both 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 CPCS phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.

Original languageEnglish (US)
Pages (from-to)93-97
Number of pages5
JournalNature Medicine
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

Fingerprint

Oligodendroglia
Brain
Stem Cells
Neural Cell Adhesion Molecules
Myelin Basic Protein
Prosencephalon
Sorting
Compaction
Fluorescence
Cells
Color
Phenotype
Myelin Sheath
Cell Extracts
Astrocytes
Axons
Flow Cytometry
Tissue Donors
Newborn Infant
Pregnancy

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Windrem, M. S., Nunes, M. C., Rashbaum, W. K., Schwartz, T. H., Goodman, R. A., McKhann, G., ... Goldman, S. A. (2004). Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nature Medicine, 10(1), 93-97. https://doi.org/10.1038/nm974

Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. / Windrem, Martha S.; Nunes, Marta C.; Rashbaum, William K.; Schwartz, Theodore H.; Goodman, Robert A.; McKhann, Guy; Roy, Neeta; Goldman, Steven A.

In: Nature Medicine, Vol. 10, No. 1, 01.01.2004, p. 93-97.

Research output: Contribution to journalArticle

Windrem, MS, Nunes, MC, Rashbaum, WK, Schwartz, TH, Goodman, RA, McKhann, G, Roy, N & Goldman, SA 2004, 'Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain', Nature Medicine, vol. 10, no. 1, pp. 93-97. https://doi.org/10.1038/nm974
Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann G et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nature Medicine. 2004 Jan 1;10(1):93-97. https://doi.org/10.1038/nm974
Windrem, Martha S. ; Nunes, Marta C. ; Rashbaum, William K. ; Schwartz, Theodore H. ; Goodman, Robert A. ; McKhann, Guy ; Roy, Neeta ; Goldman, Steven A. / Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. In: Nature Medicine. 2004 ; Vol. 10, No. 1. pp. 93-97.
@article{70ed29832d194406b37870b659c26cfa,
title = "Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain",
abstract = "Both late-gestation and adult human forebrain both 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 CPCS phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.",
author = "Windrem, {Martha S.} and Nunes, {Marta C.} and Rashbaum, {William K.} and Schwartz, {Theodore H.} and Goodman, {Robert A.} and Guy McKhann and Neeta Roy and Goldman, {Steven A.}",
year = "2004",
month = "1",
day = "1",
doi = "10.1038/nm974",
language = "English (US)",
volume = "10",
pages = "93--97",
journal = "Nature Medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain

AU - Windrem, Martha S.

AU - Nunes, Marta C.

AU - Rashbaum, William K.

AU - Schwartz, Theodore H.

AU - Goodman, Robert A.

AU - McKhann, Guy

AU - Roy, Neeta

AU - Goldman, Steven A.

PY - 2004/1/1

Y1 - 2004/1/1

N2 - Both late-gestation and adult human forebrain both 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 CPCS phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.

AB - Both late-gestation and adult human forebrain both 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 CPCS phenotypes mediated the extensive and robust myelination of congenitally dysmyelinated host brain, although their differences suggested their use for different disease targets.

UR - http://www.scopus.com/inward/record.url?scp=1542336187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1542336187&partnerID=8YFLogxK

U2 - 10.1038/nm974

DO - 10.1038/nm974

M3 - Article

C2 - 14702638

AN - SCOPUS:1542336187

VL - 10

SP - 93

EP - 97

JO - Nature Medicine

JF - Nature Medicine

SN - 1078-8956

IS - 1

ER -