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 journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
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 -