Neural stem cell response to endothelial-derived extracellular matrix produced by hemodynamically stimulated endothelial cells

This study demonstrates that adult neural stem cells (NSC) exhibit a differential response to endothelial cell (EC) derived extracellular matrix (ECM) produced under hemodynamic flow compared to statically produced ECM. In vivo, NSC reside in close proximity to blood vessels, suggesting that EC-produced factors may influence NSC fate. In vitro, it has been demonstrated that soluble factors released by EC stimulate self-renewal and inhibit differentiation of embryonic NSC [1]. However, NSC response to EC derived products produced under hemodynamic stimulation has not been explored In this work, we examined NSC response to EC produced extracellular matrix. Briefly, confluent mouse brain microvascular EC were cultured dynamically (exposed to shear stress (10 dynes/cm²)) or statically and the cells were chemically-lysed to isolate the EC derived ECM. Thick ECM substrates were generated for subsequent NSC fate studies. Adult primary murine NSC were isolated from the sub-ventricular zone, cultured as neurospheres, and dissociated onto the ECM substrates. NSC attached, spread, and infiltrated the dynamically produced ECM, while the statically produced ECM generated only small neurospheres at the ECM surface. This work will generate a better understanding of the NSC response to physiologically relevant EC derived ECM cues.