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Related Experiment Video

Updated: Jun 23, 2025

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Self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes.

Dennis M Nahon1, Marc Vila Cuenca2, Francijna E van den Hil1

  • 1Department of Anatomy and Embryology, Leiden University Medical Centre, 2333ZA Leiden, the Netherlands.

Stem Cell Reports
|June 14, 2024
PubMed
Summary

Human induced pluripotent stem cells (hiPSCs) create astrocytes for blood-brain barrier models. Astrocytes initially disrupted vascular networks but fluid flow and cAMP signaling restored organization and reduced permeability.

Keywords:
BBBblood-brain barrierhiPSC-AstrohiPSC-ECshiPSC-derived astrocyteshiPSC-derived endothelial cellshuman induced pluripotent stem cellsmicrofluidicsorgan-on-chipvessel-on-chip

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Area of Science:

  • Neuroscience
  • Biotechnology
  • Vascular Biology

Background:

  • The blood-brain barrier (BBB) is crucial for central nervous system homeostasis, regulating molecule transport.
  • Current BBB models often use primary brain cells, limiting scalability and reproducibility.
  • Human induced pluripotent stem cells (hiPSCs) offer a promising alternative cell source for disease modeling.

Purpose of the Study:

  • To investigate the use of hiPSC-derived astrocytes in a 3D vessel-on-chip (VoC) model for studying the blood-brain barrier.
  • To assess the impact of hiPSC-derived astrocytes on microvascular network formation and function within the VoC model.

Main Methods:

  • Self-organized microvascular networks were constructed using hiPSC-derived endothelial cells (ECs), human brain vascular pericytes, and hiPSC-derived astrocytes in a fibrin hydrogel.
  • The 3D VoC model was subjected to continuous fluid perfusion and cyclic AMP (cAMP) signaling activation.
  • Vascular organization and permeability were assessed, along with the expression of key BBB-related proteins.

Main Results:

  • hiPSC-derived ECs and pericytes formed microvascular networks, but the addition of hiPSC-derived astrocytes initially disrupted this formation.
  • Continuous fluid perfusion and cAMP signaling activation rescued vascular organization and decreased vascular permeability.
  • Astrocytes did not significantly alter the expression of proteins involved in junction formation, transport, or extracellular matrix.

Conclusions:

  • hiPSC-derived astrocytes can be incorporated into 3D VoC models, but their presence can initially impede microvascular network formation.
  • Fluid perfusion and cAMP signaling are critical for restoring vascular integrity and function in this model.
  • The study suggests that hiPSC-derived ECs in this 3D VoC model may not fully achieve a BBB-like phenotype without further optimization.