Cells (Apr 2020)

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

  • Annalise Di Marco,
  • Domenico Vignone,
  • Odalys Gonzalez Paz,
  • Ivan Fini,
  • Maria Rosaria Battista,
  • Antonella Cellucci,
  • Elena Bracacel,
  • Giulio Auciello,
  • Maria Veneziano,
  • Vinod Khetarpal,
  • Mark Rose,
  • Alessandro Rosa,
  • Isabelle Gloaguen,
  • Edith Monteagudo,
  • Todd Herbst,
  • Celia Dominguez,
  • Ignacio Muñoz-Sanjuán

DOI
https://doi.org/10.3390/cells9040994
Journal volume & issue
Vol. 9, no. 4
p. 994

Abstract

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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).

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