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IPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds

ABSTRACT: iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds

PROVIDER: PRJNA505675 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8192745_1.fastq.gz	Fastqsanger.gz
	SRR8192745_2.fastq.gz	Fastqsanger.gz
	SRR8192746_1.fastq.gz	Fastqsanger.gz
	SRR8192746_2.fastq.gz	Fastqsanger.gz

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iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds

Project description:We describe the construction a 3D blood-brain barrier model comprised of iPSC-derived brain endothelium cultured in channels within gelatin hydrogels. The iPSC-derived brain endothelium displays key features of the blood-brain barrier phenotype, including tight junction formation, efflux transporter activity, low paracellular permeability, and suppressed levels of transcytosis compared to non-blood-brain barrier endothelial controls. Collectively, this work provides the foundation for a fully human, biomimetic neurovascular model to study BBB in health and disease.

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iPSC-Derived Brain Endothelium Exhibits Stable, Long-Term Barrier Function in Perfused Hydrogel Scaffolds.

Project description:There is a profound need for functional, biomimetic in vitro tissue constructs of the human blood-brain barrier and neurovascular unit (NVU) to model diseases and identify therapeutic interventions. Here, we show that induced pluripotent stem cell (iPSC)-derived human brain microvascular endothelial cells (BMECs) exhibit robust barrier functionality when cultured in 3D channels within gelatin hydrogels. We determined that BMECs cultured in 3D under perfusion conditions were 10-100 times less permeable to sodium fluorescein, 3 kDa dextran, and albumin relative to human umbilical vein endothelial cell and human dermal microvascular endothelial cell controls, and the BMECs maintained barrier function for up to 21 days. Analysis of cell-cell junctions revealed expression patterns supporting barrier formation. Finally, efflux transporter activity was maintained over 3 weeks of perfused culture. Taken together, this work lays the foundation for development of a representative 3D in vitro model of the human NVU constructed from iPSCs.

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