Vasculature cells control neuroglial co-localization and synaptic connection in a central nervous system tissue mimic system.

Despite the development of neural tissue differentiation methods using a wide variety of stem cells and compartments, there is no standardized strategy for establishing synapses. As the neuronal network is developed in parallel with blood vessel angiogenesis in the central nervous system (CNS) from the embryonic period, we examined neuron-astrocyte-vasculature interactions to understand the effect of the vasculature on the development and stabilization of neurological morphogenesis. We generated a cellular co-culture module targeting the CNS that was embedded in a collagen-based extracellular matrix (ECM) gel. Our neuron-astrocyte-vascular complex module identified the neurological co-localization effect by endothelial cells, as well as the pericyte-induced improvement of synaptic connections. Furthermore, it was suggested that the PDGF, BDNF, IGF, and WNT/BMP pathways were upregulated in synaptic connections enhanced conditions, which are composed of neurexin. These results suggest that the integrity of the vasculature cells in the CNS is important for the establishment of neuronal networks and for synapse connection.