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Neuronally expressed stem cell factor induces neural stem cell migration to
areas of brain injury
Lixin Sun, Jeongwu Lee and Howard A. Fine
Neuro-Oncology Branch, National Cancer Institute, National
Institutes of Neurological Disorder and Stroke, NIH, Bethesda, Maryland, USA.
Address correspondence: Howard A. Fine, Neuro-Oncology
Branch, National Cancer Institute, National Institutes of Neurological Disorder
and Stroke, NIH, The Block Building, Room 225, 9030 Old Georgetown Road,
Bethesda, Maryland 20892-8200, USA. Phone: (301) 402-6383; Fax: (301) 480-2246;
E-mail: hfine@mail.nih.gov.
Received for publication September 9, 2003, and accepted in
revised form February 17, 2004.
Neural stem/progenitor cell (NSPC) migration toward sites of damaged
central nervous system (CNS) tissue may represent an adaptive
response for the purpose of limiting and/or repairing damage.
Little
is known of the mechanisms responsible for this migratory response.
We constructed a cDNA library of injured mouse forebrain using
subtractive suppression hybridization (SSH) to identify genes that
were selectively upregulated in the injured hemisphere.
We
demonstrate that stem cell factor (SCF) mRNA and protein are highly
induced in neurons within the zone of injured brain.
Additionally,
the SCF receptor c-kit is expressed on NSPCs in vitro and in vivo.
Finally, we demonstrate that recombinant SCF induces potent NSPC
migration in vitro and in vivo through the activation of c-kit on
NSPCs.
These data suggest that the SCF/c-kit pathway is involved in
the migration of NSPCs to sites of brain injury and that SCF may
prove useful for inducing progenitor cell recruitment to specific
areas of the CNS for cell-based therapeutic strategies.
Copyright ©2004 by the American Society for Clinical
Investigation
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