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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

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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 2

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Distribution of SCF in the injured forebrain. (A_G) Sections were immuno...
Distribution of SCF in the injured forebrain. (A_G) Sections were immunostained with an Ab against SCF and were visualized with DAB (brown). Counterstaining was done with hematoxylin (blue). (A) In the normal cortex, SCF-positive cells exist mainly in the surface of the cortex, in layers I and II. (B) In the “freeze-injured” forebrain, the distribution of SCF-staining cells include the whole depth of cortex, with intensively SCF-positive cells in the layers III, IV. (C and D) Magnified images of the black boxes in A and B, respectively. Abundant SCF-staining cells were observed in the injured area indicated by arrows in D. (E and F) SCF expression was also present in the SVZ of injured brain (F) but was not detectable in the control SVZ (E). (G) Large numbers of SCF-staining cells were present around the injury (boxes I and II), while the SCF-positive cells decreased with increasing distance away from the site of injury (boxes III and IV). Bottom row, higher-magnification views (∞200) of each section as indicated by the arrows. Boxes I_IV are schematic representations of the areas used to quantify cell numbers. Scale bar (shown in A): A and B, 200 ∝m; C_F, 50 ∝m; G, main image, 250 ∝m, and higher magnifications, 70 ∝m. Str, striatum. (H) Quantification of SCF positive cells in boxes I_IV of G. The SCF-positive cells are presented as a percentage of the total cell number for each section. Comparisons are corrected for surface area and total cells in the section. Statistical differences were determined by comparison of boxes III and IV with box I (*P < 0.05).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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