Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells

Understanding the function of the blood–brain barrier (BBB) in health and disease, as well as improving drug delivery across the BBB, remains a critical priority in neuroscience research. However, current in vitro models of the BBB have become increasingly complex and challenging to implement. In th...

Full description

Saved in:
Bibliographic Details
Main Authors: Andrea Margari, Simon Konig, Vignesh Jayarajan, Silvia Rizzato, Giuseppe Maruccio, Emad Moeendarbary
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/14/11/759
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850128936909930496
author Andrea Margari
Simon Konig
Vignesh Jayarajan
Silvia Rizzato
Giuseppe Maruccio
Emad Moeendarbary
author_facet Andrea Margari
Simon Konig
Vignesh Jayarajan
Silvia Rizzato
Giuseppe Maruccio
Emad Moeendarbary
author_sort Andrea Margari
collection DOAJ
description Understanding the function of the blood–brain barrier (BBB) in health and disease, as well as improving drug delivery across the BBB, remains a critical priority in neuroscience research. However, current in vitro models of the BBB have become increasingly complex and challenging to implement. In this study, we present a simplified microfluidic BBB model in which human umbilical vein endothelial cells (HUVECs) are cultured as a monolayer along a fibrin gel containing human pericytes and astrocytes. Remarkably, within just three days, the 3D co-culture significantly enhanced barrier formation and upregulated the expression of tight-junction proteins in HUVECs. These findings demonstrate that HUVECs, which have been extensively used for over 50 years to study vascular endothelium due to their ease of isolation and culture, can adapt their phenotype towards that of BBB endothelial cells under appropriate conditions. This microfluidic BBB model offers a valuable tool for drug development and for advancing our understanding of BBB physiology in both health and disease contexts.
format Article
id doaj-art-973bafccef574259835384b2b7bba2df
institution OA Journals
issn 2073-4409
language English
publishDate 2025-05-01
publisher MDPI AG
record_format Article
series Cells
spelling doaj-art-973bafccef574259835384b2b7bba2df2025-08-20T02:33:08ZengMDPI AGCells2073-44092025-05-01141175910.3390/cells14110759Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial CellsAndrea Margari0Simon Konig1Vignesh Jayarajan2Silvia Rizzato3Giuseppe Maruccio4Emad Moeendarbary5Department of Mechanical Engineering, University College London, London WC1E 6BT, UKDepartment of Mechanical Engineering, University College London, London WC1E 6BT, UKDepartment of Mechanical Engineering, University College London, London WC1E 6BT, UKOmnics Research Group, Department of Mathematics and Physics, University of Salento, CNR-Institute of Nanotechnology, INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, ItalyOmnics Research Group, Department of Mathematics and Physics, University of Salento, CNR-Institute of Nanotechnology, INFN Sezione di Lecce, Via per Monteroni, 73100 Lecce, ItalyDepartment of Mechanical Engineering, University College London, London WC1E 6BT, UKUnderstanding the function of the blood–brain barrier (BBB) in health and disease, as well as improving drug delivery across the BBB, remains a critical priority in neuroscience research. However, current in vitro models of the BBB have become increasingly complex and challenging to implement. In this study, we present a simplified microfluidic BBB model in which human umbilical vein endothelial cells (HUVECs) are cultured as a monolayer along a fibrin gel containing human pericytes and astrocytes. Remarkably, within just three days, the 3D co-culture significantly enhanced barrier formation and upregulated the expression of tight-junction proteins in HUVECs. These findings demonstrate that HUVECs, which have been extensively used for over 50 years to study vascular endothelium due to their ease of isolation and culture, can adapt their phenotype towards that of BBB endothelial cells under appropriate conditions. This microfluidic BBB model offers a valuable tool for drug development and for advancing our understanding of BBB physiology in both health and disease contexts.https://www.mdpi.com/2073-4409/14/11/759blood–brain barrier (BBB)in vitro modelhuman umbilical vein endothelial cells (HUVECs)endothelial cell biology
spellingShingle Andrea Margari
Simon Konig
Vignesh Jayarajan
Silvia Rizzato
Giuseppe Maruccio
Emad Moeendarbary
Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
Cells
blood–brain barrier (BBB)
in vitro model
human umbilical vein endothelial cells (HUVECs)
endothelial cell biology
title Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
title_full Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
title_fullStr Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
title_full_unstemmed Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
title_short Examining Stromal Cell Interactions in an In Vitro Blood–Brain Barrier Model with Human Umbilical Vein Endothelial Cells
title_sort examining stromal cell interactions in an in vitro blood brain barrier model with human umbilical vein endothelial cells
topic blood–brain barrier (BBB)
in vitro model
human umbilical vein endothelial cells (HUVECs)
endothelial cell biology
url https://www.mdpi.com/2073-4409/14/11/759
work_keys_str_mv AT andreamargari examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells
AT simonkonig examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells
AT vigneshjayarajan examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells
AT silviarizzato examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells
AT giuseppemaruccio examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells
AT emadmoeendarbary examiningstromalcellinteractionsinaninvitrobloodbrainbarriermodelwithhumanumbilicalveinendothelialcells