Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model
- 9 February 2021
- journal article
- research article
- Published by SAGE Publications in Journal of Cerebral Blood Flow & Metabolism
- Vol. 41 (9), 2201-2215
- https://doi.org/10.1177/0271678x21992638
Abstract
Microfluidic lab-on-a-chip (LOC) devices allow the study of blood-brain barrier (BBB) properties in dynamic conditions. We studied a BBB model, consisting of human endothelial cells derived from hematopoietic stem cells in co-culture with brain pericytes, in an LOC device to study fluid flow in the regulation of endothelial, BBB and glycocalyx-related genes and surface charge. The highly negatively charged endothelial surface glycocalyx functions as mechano-sensor detecting shear forces generated by blood flow on the luminal side of brain endothelial cells and contributes to the physical barrier of the BBB. Despite the importance of glycocalyx in the regulation of BBB permeability in physiological conditions and in diseases, the underlying mechanisms remained unclear. The MACE-seq gene expression profiling analysis showed differentially expressed endothelial, BBB and glycocalyx core protein genes after fluid flow, as well as enriched pathways for the extracellular matrix molecules. We observed increased barrier properties, a higher intensity glycocalyx staining and a more negative surface charge of human brain-like endothelial cells (BLECs) in dynamic conditions. Our work is the first study to provide data on BBB properties and glycocalyx of BLECs in an LOC device under dynamic conditions and confirms the importance of fluid flow for BBB culture models.Keywords
This publication has 37 references indexed in Scilit:
- Transcriptional Profiling of Human Brain Endothelial Cells Reveals Key Properties Crucial for Predictive In Vitro Blood-Brain Barrier ModelsPLOS ONE, 2012
- Translocating the blood-brain barrier using electrostaticsFrontiers in Cellular Neuroscience, 2012
- The role of shear stress in Blood-Brain Barrier endothelial physiologyBMC Neuroscience, 2011
- The Mouse Blood-Brain Barrier Transcriptome: A New Resource for Understanding the Development and Function of Brain Endothelial CellsPLOS ONE, 2010
- Structure and function of the blood–brain barrierNeurobiology of Disease, 2010
- CNS Delivery Via Adsorptive TranscytosisThe AAPS Journal, 2008
- Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stressAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- The endothelial glycocalyx: composition, functions, and visualizationPflügers Archiv - European Journal of Physiology, 2007
- Gene Expression Omnibus: NCBI gene expression and hybridization array data repositoryNucleic Acids Research, 2002
- Flow-dependent Regulation of Gene Expression in Vascular Endothelial Cells.Japanese Heart Journal, 1996