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Differential fate of multipotent and lineage-restricted neural precursors following transplantation into the adult CNS

Published online by Cambridge University Press:  25 October 2004

ANGELO C. LEPORE
Affiliation:
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
STEVEN S.W. HAN
Affiliation:
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
CARLA J. TYLER-POLSZ
Affiliation:
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA
JINGLI CAI
Affiliation:
Laboratory of Neuroscience, NIA, Baltimore, MD, USA
MAHENDRA S. RAO
Affiliation:
Laboratory of Neuroscience, NIA, Baltimore, MD, USA
ITZHAK FISCHER
Affiliation:
Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA

Abstract

Multiple classes of precursor cells have been isolated and characterized from the developing spinal cord including multipotent neuroepithelial (NEP) stem cells and lineage-restricted precursors for neurons (NRPs) and glia (GRPs). We have compared the survival, differentiation and integration of multipotent NEP cells with lineage-restricted NRPs and GRPs using cells isolated from transgenic rats that express the human placental alkaline phosphatase gene. Our results demonstrate that grafted NEP cells survive poorly, with no cells observed 3 days after transplant in the adult hippocampus, striatum and spinal cord, indicating that most CNS regions are not compatible with transplants of multipotent cells derived from fetal CNS. By contrast, at 3 weeks and 5 weeks post-engraftment, lineage-restricted precursors showed selective migration along white-matter tracts and robust survival in all three CNS regions. The grafted precursors expressed the mature neuronal markers NeuN and MAP2, the astrocytic marker GFAP, the oligodendrocytic markers RIP, NG2 and Sox-10, and the synaptic marker synaptophysin. Similar behavior was observed when these precursors were transplanted into the injured spinal cord. Predifferentiated, multipotent NEP cells also survive and integrate, which indicates that lineage-restricted CNS precursors are well suited for transplantation into the adult CNS and provide a promising cellular replacement candidate.

Type
Research Article
Copyright
© Cambridge University Press 2004

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