Brain Endothelial Cells Regulate Neural Stem Cell Maintenance by Consuming Growth Factors in a Reconstituted Vascular Neural Stem Cell Niche

초록

Neural stem cell (NSC) fate is tightly controlled by the surrounding vascular niche. While endothelial regulation of NSCs has been suggested, mechanistic understanding in a three-dimensional (3D) context remains limited. We engineered a 3D microfluidic vascular niche by co-culturing NSCs with brain endothelial cells (bECs) in an extracellular matrix hydrogel. To assess context-dependent regulation, NSCs were maintained under three defined media conditions (basal, differentiation-inducing, and proliferation-inducing with or without growth factors). Niche regulation was quantified through ELISA-based growth factor measurements combined with a transport-consumption computational model. bECs exerted context-dependent control: they enhanced Nestin expression and beta-catenin activity in basal and differentiation media, while suppressing self-renewal markers under growth factor-rich conditions by selectively depleting bFGF. These effects paralleled changes in viability and colony formation, providing convergent evidence of endothelial homeostatic regulation. Unlike prior 2D or conditioned-medium studies, this work establishes a chip-based, quantitative framework for dissecting vascular-NSC interactions in 3D. By directly coupling experimental measurements with computational modeling, we identify endothelial growth factor consumption as a mechanistic determinant of NSC fate. This biochip thus provides both fundamental insight and a versatile platform for regenerative and disease modeling applications.

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