Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury
Lixin Sun, … , Jeongwu Lee, Howard A. Fine
Lixin Sun, … , Jeongwu Lee, Howard A. Fine
Published May 1, 2004
Citation Information: J Clin Invest. 2004;113(9):1364-1374. https://doi.org/10.1172/JCI20001.
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Article Neuroscience

Neuronally expressed stem cell factor induces neural stem cell migration to areas of brain injury

Abstract

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.

Authors

Lixin Sun, Jeongwu Lee, Howard A. Fine

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Figure 5

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SCF/c-kit pathway is involved in injury-induced NSPC migration. (A) SCF-...
SCF/c-kit pathway is involved in injury-induced NSPC migration. (A) SCF-induced c-kit tyrosine phosphorylation (Tyr-P) was detected by immunoprecipitation (IP) and immunoblot (IB). The 120-kDa and 140-kDa bands represent the c-kit proteins in the human and mouse NSPCs. Lane 1, SCF treatment; lane 2, untreated control; lane 3, pretreatment of NSPCs with ACK45 c-kit_blocking Ab before SCF treatment. (B) Tissue lysates from injured and normal mouse forebrain were used to stimulate migration of mouse NSPCs (with or without pretreatment with ACK45 blocking Ab) in the Boyden chamber migration assay. Relative fluorescence units (RFU) correlated with the number of migrated cells. NSPC migration was significantly induced by injured brain lysates compared with normal brain lysates (*P < 0.05). The chemotactic effect of injured brain lysates was nearly completely abolished when NSPCs were pretreated with the c-kit_blocking Ab (*P < 0.05). Error bars represent SEM. These are representative experiments and similar results were obtained from at least three independent experiments.