Chemotactic Responses of Neural Stem Cells to SDF-1α Correlate Closely with Their Differentiation Status

Abstract

Chemotaxis of neural stem/progenitor cells (NSCs) is regulated by a variety of factors, and much effort has been devoted to the delineation of factors that are involved in NSC migration. However, the relationship between NSC chemotactic migration and differentiation remains uncharacterized. In the present study, by comparing the transfilter migration rate, single-cell migration speed, and directional efficiency of NSCs in stromal cell-derived factor-1 alpha (SDF-1α)-induced Boyden chamber and Dunn chamber chemotaxis assays, we demonstrate that NSCs in varying differentiation stages possess different migratory capacity. Furthermore, F-actin microfilament reorganization upon stimulation varies greatly among separate differentiation states. We show that signaling pathways involved in NSC migration, such as PI3K/Akt and mitogen-activated protein kinase (MAPK) (ERK1/2, JNK, and p38 MAPK) pathways, are differentially activated by SDF-1α among each NSC differentiation stages, and the extent to which these pathways participate in cell chemotaxis exhibits a differentiation stage-dependent manner. Taken together, these results suggest that the differentiation of NSCs influences their chemotactic responses to SDF-1α, providing new insight into the optimization of the therapeutic efficacy of NSCs for neural regeneration and nerve repair after injury.

Neural Differentiation of Mesenchymal Stem Cells Influences Their Chemotactic Responses to Stromal Cell-Derived Factor-1α

“…There is evidence showing that some growth factors at high concentrations inhibit cell migration (Liang et al 2005). Consistently, our previous data demonstrate that the migratory response of neural stem cells to SDF-1a showed a typical biphasic dose-response curve (Chen et al 2014). All these findings indicate that MSCs at varying levels of Many studies have shown that PI3K/Akt and MAPK signaling pathways mediate cell migration induced by chemokines or cytokines (Bullone et al 2013;Yang et al 2013;Segarra et al 2006).…”

SDF-1/CXCR4 axis induces human dental pulp stem cell migration through FAK/PI3K/Akt and GSK3β/β-catenin pathways

“…Previous studies have identified that PI3K is involved in multiple stem cell migration40. The same phenomenon has also been demonstrated in leukemic cell lines55 and neural precursor cells56. The increased MSC migration by SDF-1 and hypoxia were both mediated by PI3K/Akt pathway57, which could be significantly attenuated by PI3K inhibitor.…”

SDF-1 and CXCR4 play an important role in adult SVZ lineage cell proliferation and differentiation

“…Several studies have confirmed the variable nature of the effects elicited by SDF-1 and the dependency of associated effects on the differentiation status of the responding cell (Chen et al, 2014;Kokovay et al, 2010); however, the molecular mechanisms that underpin these reactions are unclear. To explore the expression patterns associated with CXCR4 in SVZ in vivo, we performed immunohistochemical analyses on SVZ whole mounts and observed that the immune stain signal was weaker from DCX-positive neuroblasts than from GFAP-positive astrocytes or type B NPCs.…”

“…Adult SVZ lineage cells have been observed to locate to, and subsequently leave, vascular niches because of differential responses to SDF1/CXCR4 signaling (Kokovay et al, 2010). More recent studies by Chen revealed that SDF-1α elicits different chemotactic effects on NPCs depending on their differentiation status (Chen et al, 2014). These findings indicate that SDF-1 affects each subpopulation of NPCs differently and the molecular mechanisms underpinning these events remain to be elucidated.…”