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Engineered Perineural Vascular Plexus for Modeling Developmental Toxicity.

Gaurav Kaushik¹, Kartik Gupta², Victoria Harms¹

¹Department of Orthopedics and Rehabilitation, University of Wisconsin-Madison, 1111 Highland Ave., WIMR 5418, Madison, WI, 53705, USA.

Advanced Healthcare Materials

|July 3, 2020

Summary

This summary is machine-generated.

This study developed a novel in vitro model of the human brain's perineural vascular plexus (PNVP) using stem cells. The model accurately predicts how developmental toxicants impact brain development and vascular network formation.

Keywords:

developmental toxicity engineered organoids human microphysiological systems microfluidics devices synthetic hydrogels

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Area of Science:

Neuroscience
Developmental Biology
Toxicology

Background:

Developing accurate in vitro models of the human brain is crucial for understanding toxicant effects.
The perineural vascular plexus (PNVP) is a key structure in embryonic brain development.

Purpose of the Study:

To develop and validate an in vitro model of the human perineural vascular plexus (PNVP).
To assess the utility of this model in predicting developmental toxicity.

Main Methods:

Co-culture of human embryonic stem cell-derived endothelial cells, neural progenitor cells, microglia, and pericytes in microfluidic devices.
Characterization of vascular plexus and neuronal layer formation.
Exposure to developmental toxicants and assessment of cellular migration, network formation, and secretion levels.

Main Results:

The model successfully recapitulated PNVP structure and function, including neurotrophic factor secretion.
Developmental toxicants significantly disrupted endothelial cell and microglia migration, vascular network formation, and VEGFA secretion.
Quantification of 3D cell migration, metabolic activity, and cytotoxicity provided relevant toxicity data.

Conclusions:

The developed PNVP model serves as a valuable tool for predicting developmental toxicity.
This in vitro system offers a physiologically relevant platform for studying toxicant impacts on the developing human brain.