Modern Methods and Materials for Modeling Brain Tissue and Blood-Brain Barrier In Vitro

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Neurovascular unit (NVU) is an ensemble of brain cells (cerebral endothelial cells, astrocytes, pericytes, neurons, and microglia), which regulates processes of transport through the blood-brain barrier (BBB) and controls local microcirculation and intercellular metabolic coupling. Dysfunction of NVU contributes to numerous types of central nervous system pathology. NVU pathophysiology has been extensively studied in various animal models of brain disorders, and there is growing evidence that modern approaches utilizing in vitro models are very promising for the assessment of intercellular communications within the NVU. Development of NVU‑on-chip or BBB‑on-chip as well as 3D NVU and brain tissue models suggests novel clues to understanding cell-to-cell interactions critical for brain functional activity, being therefore very important for translational studies, drug discovery, and development of novel analytical platforms. One of the mechanisms controlled by NVU activity is neurogenesis in highly specialized areas of brain (neurogenic niches, NNs), which are well-equipped for the maintenance of stem/progenitor cell pool and proliferation, differentiation, and migration of newly formed neuronal and glial cells. Specific properties of brain microvascular endothelial cells, particularly, high content of mitochondria, are important for establishment of vascular support in NVU and NNs. Metabolic activity of cells within NNs and NVU contributes to maintaining intercellular communications critical for the multicellular module integrity. We will discuss modern approaches to development of optimal microenvironment for in vitro BBB, NVU and NN models with the special focus on neuroengineering and bioprinting potentials