A human blood-brain barrier model reveals pericytes as critical regulators of viral neuroinvasion
Alexsia Richards, Andrew Khalil, Punam Bisht, Troy W. Whitfield, Xinlei Gao, David Mooney, Lee Gehrke, Rudolf Jaenisch
TL;DR
This study shows that pericytes, generated from stem cells, help protect the blood-brain barrier from viral infections and reduce the spread of viruses to the brain.
Contribution
The study introduces a serum-free method to generate pericytes from stem cells and reveals their role in limiting viral neuroinvasion.
Findings
NCC-PCs maintain endothelial barrier integrity during viral infection.
Pericytes reduce the spread of viral infection to the central nervous system.
Pericytes exhibit polarized virus release in a Transwell system.
Abstract
The blood-brain barrier (BBB) plays a vital role in regulating the passage of biomolecules between the bloodstream and the central nervous system (CNS) while also protecting the CNS from pathogens. Pericytes reside at the interface between endothelial cells and the brain parenchyma. These cells are critical for maintaining BBB integrity and regulating vessel permeability, blood flow, and immune cell migration. In this study, we developed a serum-free protocol to generate neural crest cell-derived pericytes (NCC-PCs) from human pluripotent stem cells (hPSCs). These NCC-PCs can be co-cultured with hPSC-derived brain microvascular endothelial cells (BMECs) in a co-culture BBB model that recapitulates the in vivo cellular interactions at the BBB. We used this model to evaluate the pathological consequences of BBB exposure to highly neuroinvasive flaviviruses. Our results identify a…
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Taxonomy
TopicsBarrier Structure and Function Studies · Cerebrospinal fluid and hydrocephalus · Neurogenesis and neuroplasticity mechanisms