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 7

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SCF-stimulated progenitor cell migration in vivo. (A) Quantification of ...
SCF-stimulated progenitor cell migration in vivo. (A) Quantification of BrdU-labeled cells in the injected areas (1.5 mm2) and in the contralateral side of the brain. Significantly more BrdU-labeled cells were seen in the SCF-injected area than in the PBS-injected area or in the contralateral side of the SCF-injected brain (P < 0.001; n = 6). inj., injection side; contra., side contralateral to SCF injection. (B) Representative images of BrdU staining in the cortical areas. (C) Schematic diagram of the brain used to examine the response of NPSC to rmSCF is shown. The blue arrow indicates the intracerebral injection track (as described in Methods). (D) Normal distribution of BrdU-positive cells. These cells were detected mainly in the SVZ prior to SCF injection and were also positive for phospho-histone H3 staining (p-H3). (E and F) Immunohistochemistry of SCF-injected brain with BrdU and phospho-histone H3 antibodies in LVZ (E) and SCF-injected cortex (F). (G) Nestin expression of BrdU-positive cells in the SVZ. (H) Three-dimensional digital image of the cells indicated by the arrowhead in G is shown. Upper, main, and right panels show views of the xz, xy, and yz planes, respectively. Lines represent coordinates in each plane. x axis, 23.2 ∝m; y axis, 23.2 ∝m; z axis, 11 ∝m; optical section thickness, 1.1 ∝m. Scale bar (shown in B): B, 100 ∝m; D, 64 ∝m; E and F, 32 ∝m; G, 12 ∝m.