Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury.
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.
Sun
Lixin
L
Neuro-Oncology Branch, National Cancer Institute, National Institutes of Neurological Disorder and Stroke, NIH, Bethesda, Maryland 20892-8200, USA.
Lee
Jeongwu
J
Fine
Howard A
HA
D000818:Animals; D001930:Brain Injuries / Q000209:etiology; D002465:Cell Movement; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011233:Precipitin Tests; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D019089:Stem Cell Factor / Q000378:metabolism / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D012333:RNA, Messenger; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit