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

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-1 alpha)-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-1 alpha 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-1 alpha, providing new insight into the optimization of the therapeutic efficacy of NSCs for neural regeneration and nerve repair after injury.