Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice
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Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice. / Ader, Marius; Schachner, Melitta; Bartsch, Udo.
in: EUR J NEUROSCI, Jahrgang 20, Nr. 5, 09.2004, S. 1205-10.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Integration and differentiation of neural stem cells after transplantation into the dysmyelinated central nervous system of adult mice
AU - Ader, Marius
AU - Schachner, Melitta
AU - Bartsch, Udo
PY - 2004/9
Y1 - 2004/9
N2 - Mutant mice deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn are characterized by a severely hypomyelinated central nervous system (CNS) and morphologically abnormal myelin sheaths. Despite this pronounced phenotype, MAG/Fyn-deficient mice have a normal longevity. In the present study, we took advantage of the normal life expectancy of this myelin mutant and grafted neural stem cells (NSCs) into the CNS of MAG/Fyn-deficient mice to study in short- and long-term experiments the fate of NSCs in adult dysmyelinated brains. Neural stem cells were isolated from spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro in the presence of mitogens for up to 5 weeks before they were grafted into the lateral ventricles or injected into white matter tracts. Analysis of mutant brains 3-15 weeks after intracerebroventricular transplantation of NSCs revealed only limited integration of donor cells into the host brains. However, injection of NSCs directly into white matter tracts resulted in widespread distribution of donor cells within the host tissue. Donor cells survived for at least 15 weeks in adult host brains. The majority of grafted cells populated white matter tracts and differentiated into oligodendrocytes that myelinated host axons. Results suggest that intraparenchymal transplantation of NSCs might be a strategy to reconstruct myelin in dysmyelinated adult brains.
AB - Mutant mice deficient in the myelin-associated glycoprotein (MAG) and the nonreceptor-type tyrosine kinase Fyn are characterized by a severely hypomyelinated central nervous system (CNS) and morphologically abnormal myelin sheaths. Despite this pronounced phenotype, MAG/Fyn-deficient mice have a normal longevity. In the present study, we took advantage of the normal life expectancy of this myelin mutant and grafted neural stem cells (NSCs) into the CNS of MAG/Fyn-deficient mice to study in short- and long-term experiments the fate of NSCs in adult dysmyelinated brains. Neural stem cells were isolated from spinal cords of transgenic mouse embryos ubiquitously expressing enhanced green fluorescent protein. Cells were expanded in vitro in the presence of mitogens for up to 5 weeks before they were grafted into the lateral ventricles or injected into white matter tracts. Analysis of mutant brains 3-15 weeks after intracerebroventricular transplantation of NSCs revealed only limited integration of donor cells into the host brains. However, injection of NSCs directly into white matter tracts resulted in widespread distribution of donor cells within the host tissue. Donor cells survived for at least 15 weeks in adult host brains. The majority of grafted cells populated white matter tracts and differentiated into oligodendrocytes that myelinated host axons. Results suggest that intraparenchymal transplantation of NSCs might be a strategy to reconstruct myelin in dysmyelinated adult brains.
KW - Animals
KW - Brain
KW - Brain Tissue Transplantation
KW - Cell Differentiation
KW - Cells, Cultured
KW - Demyelinating Autoimmune Diseases, CNS
KW - Female
KW - Fetal Tissue Transplantation
KW - Mice
KW - Mice, Transgenic
KW - Myelin-Associated Glycoprotein
KW - Neurons
KW - Pregnancy
KW - Proto-Oncogene Proteins
KW - Proto-Oncogene Proteins c-fyn
KW - Stem Cell Transplantation
KW - Comparative Study
KW - Journal Article
U2 - 10.1111/j.1460-9568.2004.03577.x
DO - 10.1111/j.1460-9568.2004.03577.x
M3 - SCORING: Journal article
C2 - 15341592
VL - 20
SP - 1205
EP - 1210
JO - EUR J NEUROSCI
JF - EUR J NEUROSCI
SN - 0953-816X
IS - 5
ER -