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Updated: Oct 20, 2025

Generation of a Human iPSC-Based Blood-Brain Barrier Chip
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A Human Neurovascular Unit On-a-Chip.

Sharon Wei Ling Lee1,2, Renato Rogosic3, Claudia Venturi4

  • 1Singapore Immunology Network (SIgN), Biomedical Sciences Institute, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore.

Methods in Molecular Biology (Clifton, N.J.)
|September 14, 2021
PubMed
Summary

Researchers created a novel microfluidic blood-brain barrier (BBB) model using human cells. This advanced model mimics the human BBB, improving drug delivery strategies for neurological diseases.

Keywords:
Blood–brain barrierHuman induced pluripotent stem cellsMicrofluidicNeurovascular unitOrganotypic model

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Area of Science:

  • Neuroscience
  • Biomedical Engineering
  • Cell Biology

Background:

  • The central nervous system (CNS) relies on the blood-brain barrier (BBB) for protection and homeostasis.
  • The BBB's restrictive nature impedes drug delivery for treating neurological disorders and brain tumors.
  • Existing in vivo and in vitro models have limitations in replicating the human BBB's environment.

Purpose of the Study:

  • To develop an advanced microfluidic model of the human neurovascular unit.
  • To overcome limitations of current models in simulating the human BBB.
  • To create a more accurate platform for studying BBB function and improving therapeutic strategies.

Main Methods:

  • Established a microfluidic device containing a co-culture of human cerebral endothelial cells (hCMEC-D3), brain pericytes (hBMVPC), astrocytes (hiPSC-AC), and neurons (hiPSC-N).
  • Utilized fluorescent cell-specific markers and confocal microscopy to visualize cellular morphology.
  • Assessed barrier function by measuring the permeation of fluorescent solutes with varying molecular weights.

Main Results:

  • Successfully cultured a multi-cellular neurovascular unit within a microfluidic system.
  • Visualized the distinct physiological morphology of endothelial cells, pericytes, astrocytes, and neurons.
  • Demonstrated selective permeability of the model to fluorescent solutes, confirming its function as a barrier.

Conclusions:

  • The developed microfluidic model effectively replicates key aspects of the human blood-brain barrier.
  • This model offers a more physiologically relevant platform for studying BBB mechanisms.
  • It holds potential for advancing drug discovery and therapeutic development for CNS diseases.