LUMC researchers develop a self-assembling 3D vessel-on-chip model with hiPSC-derived astrocytes

Watch the video of the self-assembling 3D Vessel-on-Chip model.

The blood-brain barrier (BBB) is formed through direct interactions between endothelial cells (ECs), pericytes, and astrocytes in the central nervous system. BBB dysfunction is increasingly recognized as a contributor to multiple neurodegenerative diseases. Most experimental models for the BBB rely on freshly isolated primary brain cells. Here, the researcher from the Orlova group at the LUMC, explored human induced pluripotent stem cells (hiPSCs) as a cellular source for astrocytes in a 3D vessel-on-chip (VoC).

They were able to successfully develop perfusable 3D microvascular networks containing hiPSC-derived endothelial cells, pericytes, and hiPSC-derived astrocytes within a Vessel-on-Chip device. Importantly, they confirmed that hiPSC-derived astrocytes can replace commonly used primary astrocytes, exhibiting similar phenotypes and interactions. Unexpectedly, the inclusion of hiPSC-derived astrocytes initially disrupted microvascular network formation. However, this challenge was resolved through continuous fluid perfusion or activation of cAMP signaling.

This work paves the way for further development of microvascular BBB networks which will be instrumental in investigating complex neurovascular disease.

For the full publication click here.

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