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

Celia Dominguez¹  Ignacio Muñoz-Sanjuán¹  Todd Herbst¹  Mark Rose¹  Vinod Khetarpal¹  Alessandro Rosa²  Edith Monteagudo³  Elena Bracacel³  Maria Veneziano³  Giulio Auciello⁴  Ivan Fini⁴  Odalys Gonzalez Paz⁴  Isabelle Gloaguen⁴  Domenico Vignone⁴  MariaRosaria Battista⁴  Annalise Di Marco⁴  Antonella Cellucci⁴ 

[1] CHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USA;Department of Biology and Biotechnology Charles Darwin, Sapienza University, Piazzale Aldo Moro 5, 00185 Roma RM, Italy;Drug Metabolism and Pharmacokinetics, IRBM SpA, Pomezia, 00071 Rome, Italy;High Content Biology and Screening, IRBM SpA, Pomezia, 00071 Rome, Italy;

关键词: blood brain barrier;    human induced pluripotent stem cells;    CNS;    permeability;    Huntington’s disease;   

DOI  :  10.3390/cells9040994

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown