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.

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

“…The role of SCF in the nervous system is poorly understood. However, SCF has recently been shown to stimulate neurogenesis as well as the migration of endogenous neural progenitors in vivo (Jin et al, 2002;Sun et al, 2004). These data support that SCF could be an important factor in regulating the proliferation and recruitment of endogenous progenitor cells during brain injury.…”

“…SCF, the ligand for the receptor c-kit, was a good potential candidate as previous observations have indicated its pro-survival and chemoattractant properties with regard to different types of stem cells, including NSCs (Matsui et al, 1990;Erlandsson et al, 2004;Sun et al, 2004). Using immunohistofluorescence, we found that, in sham-lesioned animals (Vehicle/DMEM or Vehicle/grafts), SCF was expressed almost exclusively in the ependymal layer of the subventricular zone (SVZ; Fig.…”

“…Endogenous neural progenitors have the ability to proliferate and/or migrate towards brain lesions in various pathological models as well as in the diseased human brain (Arvidsson et al, 2002;Curtis et al, 2003;Sun et al, 2004;Tattersfield et al, 2004). Exogenous stem cells also display an ability to migrate and survive in the lesioned parenchyma following transplantation (Eglitis et al, 1999;Mahmood et al, 2001;Imitola et al, 2004;Hill et al, 2004).…”

“…6A and B, SCF triggered the activation of c-kit in both cell types, as demonstrated by an increase in the phospho-c-kit signal, and this consequently resulted in the phosphorylation of Erk. The SCF-c-kit pathway is well known as a promoter of migration in different types of stem cells such as hematopoietic (Hassan and Zander, 1996 for review), spermatogonial (Ohta et al, 2003) and neural stem cells (Jin et al, 2002;Erlandsson et al, 2004;Sun et al, 2004). We therefore examined the possibility that the activation of the c-kit pathway led to a similar functional effect, in addition to the increased kinase activity detected biochemically.…”

Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats

“…3a). Phospho-histone H3 is a cell proliferation mitosis marker [22,23]. In 21-day-old rats, ghrelin treatment increased cells double-positive for phospho-histone H3 and insulin approximately 1.7-and 15-fold in Ghrelin and n0- Fig.…”