Reconstituting neurovascular unit based on the close relations between neural stem cells and endothelial cells: an effective method to explore neurogenesis and angiogenesis.

The discovery of neural stem cells (NSCs) and their microenvironment, the NSC niche, brought new therapeutic strategies through neurogenesis and angiogenesis for stroke and most neurodegenerative diseases, including Alzheimer's disease. Based on the close links between NSCs and endothelial cells, the integration of neurogenesis and angiogenesis of the NSC niche is also a promising area to the neurovascular unit (NVU) modeling and is now offering a powerful tool to advance our understanding of the brain. In this review, critical aspects of the NVU and model systems are discussed. First, we briefly describe the interaction of each part in the NSC niche. Second, we introduce the co-culture system, microfluidic platforms, and stem cell-derived 3D reconstitution used in NVU modeling based on the close relations between NSCs and endothelial cells, and various characteristics of cell interactions in these systems are also described. Finally, we address the challenges in modeling the NVU that can potentially be overcome by employing strategies for advanced biomaterials and stem cell co-culture use. Based on these approaches, researchers will continue to develop predictable technologies to control the fate of stem cells, achieve accurate screening of drugs for the nervous system, and advance the clinical application of NVU models.