Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin-associated glycoprotein and Fyn tyrosine kinase

Standard

Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin-associated glycoprotein and Fyn tyrosine kinase. / Ader, M; Schachner, M; Bartsch, U.

In: EUR J NEUROSCI, Vol. 14, No. 3, 08.2001, p. 561-6.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

APA

Vancouver

Bibtex

@article{c15e1e86773b4c5b89033416a9412943,
title = "Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin-associated glycoprotein and Fyn tyrosine kinase",
abstract = "We have studied in long-term experiments the fate of intraventricularly transplanted neural precursor cells in a dysmyelinated mouse brain. Precursor cells were isolated from striata or spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein (EGFP). Cells were expanded in vitro in the presence of mitogens for up to 14 weeks, and injected into the lateral ventricle of young postnatal mouse mutants deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn. The CNS of these mutants is severely hypomyelinated and most myelin sheaths display ultrastructural abnormalities. Despite this phenotype, MAG/Fyn-deficient mice have a normal longevity. Analysis of mutant brains 1 to 6 months after transplantation revealed widespread distribution of EGFP-positive cells in the recipient tissue. Grafted cells preferentially populated white matter tracts and differentiated into a variety of morphologically distinct cell types. A significant fraction of donor cells was identified as oligodendrocytes. Electron microscopic analysis revealed the presence of numerous donor-derived, ultrastructurally intact, myelin sheaths around host axons. EGFP-positive oligodendrocytes and myelin survived for up to 6 months after transplantation, the latest time point investigated. Remarkably, the number of donor-derived oligodendrocytes increased significantly with increasing time intervals after transplantation, resulting in widespread myelination of 6-month-old host brains. These long-term experiments thus demonstrate that extensive myelination of a dysmyelinated brain can be achieved after a single injection of neural precursor cells.",
keywords = "Animals, Cell Differentiation, Cell Transplantation, Central Nervous System, Demyelinating Diseases, Female, Graft Survival, Immunohistochemistry, In Situ Hybridization, Mice, Mice, Inbred C57BL, Mice, Knockout, Microscopy, Electron, Myelin Sheath, Myelin-Associated Glycoprotein, Neurons, Oligodendroglia, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-fyn, Journal Article",
author = "M Ader and M Schachner and U Bartsch",
year = "2001",
month = aug,
language = "English",
volume = "14",
pages = "561--6",
journal = "EUR J NEUROSCI",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Transplantation of neural precursor cells into the dysmyelinated CNS of mutant mice deficient in the myelin-associated glycoprotein and Fyn tyrosine kinase

AU - Ader, M

AU - Schachner, M

AU - Bartsch, U

PY - 2001/8

Y1 - 2001/8

N2 - We have studied in long-term experiments the fate of intraventricularly transplanted neural precursor cells in a dysmyelinated mouse brain. Precursor cells were isolated from striata or spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein (EGFP). Cells were expanded in vitro in the presence of mitogens for up to 14 weeks, and injected into the lateral ventricle of young postnatal mouse mutants deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn. The CNS of these mutants is severely hypomyelinated and most myelin sheaths display ultrastructural abnormalities. Despite this phenotype, MAG/Fyn-deficient mice have a normal longevity. Analysis of mutant brains 1 to 6 months after transplantation revealed widespread distribution of EGFP-positive cells in the recipient tissue. Grafted cells preferentially populated white matter tracts and differentiated into a variety of morphologically distinct cell types. A significant fraction of donor cells was identified as oligodendrocytes. Electron microscopic analysis revealed the presence of numerous donor-derived, ultrastructurally intact, myelin sheaths around host axons. EGFP-positive oligodendrocytes and myelin survived for up to 6 months after transplantation, the latest time point investigated. Remarkably, the number of donor-derived oligodendrocytes increased significantly with increasing time intervals after transplantation, resulting in widespread myelination of 6-month-old host brains. These long-term experiments thus demonstrate that extensive myelination of a dysmyelinated brain can be achieved after a single injection of neural precursor cells.

AB - We have studied in long-term experiments the fate of intraventricularly transplanted neural precursor cells in a dysmyelinated mouse brain. Precursor cells were isolated from striata or spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein (EGFP). Cells were expanded in vitro in the presence of mitogens for up to 14 weeks, and injected into the lateral ventricle of young postnatal mouse mutants deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn. The CNS of these mutants is severely hypomyelinated and most myelin sheaths display ultrastructural abnormalities. Despite this phenotype, MAG/Fyn-deficient mice have a normal longevity. Analysis of mutant brains 1 to 6 months after transplantation revealed widespread distribution of EGFP-positive cells in the recipient tissue. Grafted cells preferentially populated white matter tracts and differentiated into a variety of morphologically distinct cell types. A significant fraction of donor cells was identified as oligodendrocytes. Electron microscopic analysis revealed the presence of numerous donor-derived, ultrastructurally intact, myelin sheaths around host axons. EGFP-positive oligodendrocytes and myelin survived for up to 6 months after transplantation, the latest time point investigated. Remarkably, the number of donor-derived oligodendrocytes increased significantly with increasing time intervals after transplantation, resulting in widespread myelination of 6-month-old host brains. These long-term experiments thus demonstrate that extensive myelination of a dysmyelinated brain can be achieved after a single injection of neural precursor cells.

KW - Animals

KW - Cell Differentiation

KW - Cell Transplantation

KW - Central Nervous System

KW - Demyelinating Diseases

KW - Female

KW - Graft Survival

KW - Immunohistochemistry

KW - In Situ Hybridization

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Microscopy, Electron

KW - Myelin Sheath

KW - Myelin-Associated Glycoprotein

KW - Neurons

KW - Oligodendroglia

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-fyn

KW - Journal Article

M3 - SCORING: Journal article

C2 - 11553306

VL - 14

SP - 561

EP - 566

JO - EUR J NEUROSCI

JF - EUR J NEUROSCI

SN - 0953-816X

IS - 3

ER -