A human blood-brain barrier model reveals pericytes as critical regulators of viral neuroinvasion
Year: 2025
Type: article
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 the endothelial cells that form the vessel walls and the brain parenchyma. These cells are critical for maintaining BBB integrity and play key roles in regulating vessel permeability, blood flow, and immune cell migration. In this study, we developed a novel serum-free protocol to generate neural crest cell-derived pericytes (NCC-PCs) from human pluripotent stem cells (hPSCs). These NCC-PCs enhance BMEC barrier function and can be co-cultured with hPSC-derived brain microvascular endothelial cells (BMECs) in a contact 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 cell infection by highly neuroinvasive flaviviruses. Our results identify a previously undescribed role for NCC-PCs in maintaining BMEC barrier integrity during infection and reducing the spread of viral infection to the CNS.
Source: iScience
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,240
Funders: Foundation for the National Institutes of Health, Harvard University, Harvard University Center for AIDS Research, Massachusetts Consortium on Pathogen Readiness, National Institutes of Health, Center for AIDS Research, University of Washington, Hansjörg Wyss Institute for Biologically Inspired Engineering, Harvard University, Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, National Institute of Allergy and Infectious Diseases, National Institute of Biomedical Imaging and Bioengineering
OpenAlex ID: W4417290402