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Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System

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High content Biology and Screening, IRBM SpA, 00071 Pomezia, Italy
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Drug Metabolism and Pharmacokinetics, IRBM SpA, 00071 Pomezia, Italy
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CHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USA
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Department of Biology and Biotechnology Charles Darwin, Sapienza University, Piazzale Aldo Moro 5, 00185 Rome, Italy
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Center for Life Nano Sciences, Istituto Italiano di Tecnologica, Viale Regina Elena, 291, 00161 Rome, Italy
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(4), 994; https://doi.org/10.3390/cells9040994
Received: 12 March 2020 / Revised: 10 April 2020 / Accepted: 14 April 2020 / Published: 16 April 2020
The blood-brain barrier (BBB) is responsible for the homeostasis between the cerebral vasculature and the brain and it has a key role in regulating the influx and efflux of substances, in healthy and diseased states. Stem cell technology offers the opportunity to use human brain-specific cells to establish in vitro BBB models. Here, we describe the establishment of a human BBB model in a two-dimensional monolayer culture, derived from human induced pluripotent stem cells (hiPSCs). This model was characterized by a transendothelial electrical resistance (TEER) higher than 2000 Ω∙cm2 and associated with negligible paracellular transport. The hiPSC-derived BBB model maintained the functionality of major endothelial transporter proteins and receptors. Some proprietary molecules from our central nervous system (CNS) programs were evaluated revealing comparable permeability in the human model and in the model from primary porcine brain endothelial cells (PBECs). View Full-Text
Keywords: blood brain barrier; human induced pluripotent stem cells; CNS; permeability; Huntington’s disease blood brain barrier; human induced pluripotent stem cells; CNS; permeability; Huntington’s disease
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Di Marco, A.; Vignone, D.; Gonzalez Paz, O.; Fini, I.; Battista, M.R.; Cellucci, A.; Bracacel, E.; Auciello, G.; Veneziano, M.; Khetarpal, V.; Rose, M.; Rosa, A.; Gloaguen, I.; Monteagudo, E.; Herbst, T.; Dominguez, C.; Muñoz-Sanjuán, I. Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine Cell-Based System. Cells 2020, 9, 994.

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