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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-11-23
pubmed:abstractText
Stem cell therapy is a hope for the treatment of some childhood neurological disorders. We examined whether human neural stem cells (hNSCs) replace lost cells in a newborn mouse model of brain damage. Excitotoxic lesions were made in neonatal mouse forebrain with the N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid (QA). QA induced apoptosis in neocortex, hippocampus, striatum, white matter, and subventricular zone. This degeneration was associated with production of cleaved caspase-3. Cells immunopositive for inducible nitric oxide synthase were present in damaged white matter and subventricular zone. Three days after injury, mice received brain parenchymal or intraventricular injections of hNSCs derived from embryonic germ (EG) cells. Human cells were prelabeled in vitro with DiD for in vivo tracking. The locations of hNSCs within the mouse brain were determined through DiD fluorescence and immunodetection of human-specific nestin and nuclear antigen 7 days after transplantation. hNSCs survived transplantation into the lesioned mouse brain, as evidenced by human cell markers and DiD fluorescence. The cells migrated away from the injection site and were found at sites of injury within the striatum, hippocampus, thalamus, and white matter tracts and at remote locations in the brain. Subsets of grafted cells expressed neuronal and glial cell markers. hNSCs restored partially the complement of striatal neurons in brain-damaged mice. We conclude that human EG cell-derived NSCs can engraft successfully into injured newborn brain, where they can survive and disseminate into the lesioned areas, differentiate into neuronal and glial cells, and replace lost neurons. (c) 2005 Wiley-Liss, Inc.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0360-4012
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
592-608
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16247803-Animals, pubmed-meshheading:16247803-Animals, Newborn, pubmed-meshheading:16247803-Apoptosis, pubmed-meshheading:16247803-Brain Damage, Chronic, pubmed-meshheading:16247803-Caspase 3, pubmed-meshheading:16247803-Caspases, pubmed-meshheading:16247803-Cell Differentiation, pubmed-meshheading:16247803-Cell Line, pubmed-meshheading:16247803-Cell Proliferation, pubmed-meshheading:16247803-Disease Models, Animal, pubmed-meshheading:16247803-Germ Cells, pubmed-meshheading:16247803-Graft Survival, pubmed-meshheading:16247803-Humans, pubmed-meshheading:16247803-Mice, pubmed-meshheading:16247803-Mice, Inbred C57BL, pubmed-meshheading:16247803-Nerve Degeneration, pubmed-meshheading:16247803-Neurons, pubmed-meshheading:16247803-Neurotoxins, pubmed-meshheading:16247803-Nitric Oxide Synthase, pubmed-meshheading:16247803-Oligodendroglia, pubmed-meshheading:16247803-Prosencephalon, pubmed-meshheading:16247803-Stem Cell Transplantation, pubmed-meshheading:16247803-Stem Cells, pubmed-meshheading:16247803-Treatment Outcome
pubmed:year
2005
pubmed:articleTitle
Transplanted human embryonic germ cell-derived neural stem cells replace neurons and oligodendrocytes in the forebrain of neonatal mice with excitotoxic brain damage.
pubmed:affiliation
Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural