A Human Neurovascular Unit On-a-Chip

Sharon Wei Ling Lee, Renato Rogosic, Claudia Venturi, Manuela Teresa Raimondi, Andrea Pavesi, Giulia Adriani*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Protection of the central nervous system (CNS) and cerebral homeostasis depend upon the blood-brain barrier (BBB) functions and permeability. BBB restrictive permeability hinders drug delivery for the treatment of several neurodegenerative diseases and brain tumors. Several in vivo animal models and in vitro systems have been developed to understand the BBB complex mechanisms and aid in the design of improved therapeutic strategies. However, there are still many limitations that should be addressed to achieve the structural and chemical environment of a human BBB. We developed a microfluidic-based model of the neurovascular unit. A monolayer of human cerebral endothelial cells (hCMEC-D3) was grown and cocultured with human brain microvascular pericytes (hBMVPC), and human induced pluripotent stem cells differentiated into astrocytes (hiPSC-AC) and neurons (hiPSC-N). To visualize the physiological morphology of each cell type, we used fluorescent cell-specific markers and confocal microscopy. Permeation of fluorescent solutes with different molecular weights was measured to demonstrate that the developed BBB was selectively permeable as a functional barrier.

Original languageEnglish
Pages (from-to)107-119
Number of pages13
JournalMethods in Molecular Biology
Volume2373
DOIs
Publication statusPublished - 2022

Keywords

  • Animals
  • Blood-Brain Barrier
  • Coculture Techniques
  • Endothelial Cells
  • Humans
  • Induced Pluripotent Stem Cells
  • Lab-On-A-Chip Devices

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