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Chunk #1 — Introduction

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In Vitro Modeling of Blood-Brain Barrier with Human iPSC-Derived Endothelial Cells, Pericytes, Neurons, and Astrocytes via Notch Signaling.
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Current in vitro BBB models use brain microvessels and astrocytes isolated from non-human species such as pig, rat, or mouse (Deli et al., 2005). However, the characteristics and functions of the BBB from these species differ from that in humans (Aday et al., 2016, Hoshi et al., 2013, Syvänen et al., 2009, Warren et al., 2009). Therefore, a human-derived BBB model is needed for pre-clinical drug screening or research about human BBB physiology and pathology. Although human primary brain microvessels isolated from the brain specimens of tumors or epilepsy patients can be used, they have low availability and reproductivity (Cecchelli et al., 2007). Immortalized human brain microvessels have also been considered, but the resulting BBB models do not form strong barrier properties due to discontinuous tight junctions (Weksler et al., 2005). Endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) have been used to prepare human in vitro BBB models, but these cells must be co-cultured with primary rat astrocytes or C6 rat glioma cells for maturation of the BBB (Lippmann et al., 2012, Minami et al., 2015).