Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms

Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In t...

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Main Authors: Aisen Vivas, Julia Mikhal, Gabriela M. Ong, Anna Eigenbrodt, Andries D. van der Meer, Rene Aquarius, Bernard J. Geurts, Hieronymus D. Boogaarts
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Brain Sciences
Subjects:
Online Access:https://www.mdpi.com/2076-3425/12/5/603
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author Aisen Vivas
Julia Mikhal
Gabriela M. Ong
Anna Eigenbrodt
Andries D. van der Meer
Rene Aquarius
Bernard J. Geurts
Hieronymus D. Boogaarts
author_facet Aisen Vivas
Julia Mikhal
Gabriela M. Ong
Anna Eigenbrodt
Andries D. van der Meer
Rene Aquarius
Bernard J. Geurts
Hieronymus D. Boogaarts
author_sort Aisen Vivas
collection DOAJ
description Intracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.
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spelling doaj.art-ca43053a8d1b4b82942aa666f14b73862023-11-23T10:17:45ZengMDPI AGBrain Sciences2076-34252022-05-0112560310.3390/brainsci12050603Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial AneurysmsAisen Vivas0Julia Mikhal1Gabriela M. Ong2Anna Eigenbrodt3Andries D. van der Meer4Rene Aquarius5Bernard J. Geurts6Hieronymus D. Boogaarts7Applied Stem Cell Technologies, University of Twente, 7522 NB Enschede, The NetherlandsMultiscale Modeling and Simulation Group, Department of Applied Mathematics, University of Twente, 7522 NB Enschede, The NetherlandsMultiscale Modeling and Simulation Group, Department of Applied Mathematics, University of Twente, 7522 NB Enschede, The NetherlandsApplied Stem Cell Technologies, University of Twente, 7522 NB Enschede, The NetherlandsApplied Stem Cell Technologies, University of Twente, 7522 NB Enschede, The NetherlandsDepartment of Neurosurgery, Radboud University Medical Center, 6525 XZ Nijmegen, The NetherlandsMultiscale Modeling and Simulation Group, Department of Applied Mathematics, University of Twente, 7522 NB Enschede, The NetherlandsDepartment of Neurosurgery, Radboud University Medical Center, 6525 XZ Nijmegen, The NetherlandsIntracranial aneurysms are pouch-like extrusions from the vessels at the base of the brain which can rupture and cause a subarachnoid hemorrhage. The pathophysiological mechanism of aneurysm formation is thought to be a consequence of blood flow (hemodynamic) induced changes on the endothelium. In this study, the results of a personalized aneurysm-on-a-chip model using patient-specific flow parameters and patient-specific cells are presented. CT imaging was used to calculate CFD parameters using an immersed boundary method. A microfluidic device either cultured with human umbilical vein endothelial cells (HUVECs) or human induced pluripotent stem cell-derived endothelial cells (hiPSC-EC) was used. Both types of endothelial cells were exposed for 24 h to either 0.03 Pa or 1.5 Pa shear stress, corresponding to regions of low shear and high shear in the computational aneurysm model, respectively. As a control, both cell types were also cultured under static conditions for 24 h as a control. Both HUVEC and hiPSC-EC cultures presented as confluent monolayers with no particular cell alignment in static or low shear conditions. Under high shear conditions HUVEC elongated and aligned in the direction of the flow. HiPSC-EC exhibited reduced cell numbers, monolayer gap formation and cells with aberrant, spread-out morphology. Future research should focus on hiPSC-EC stabilization to allow personalized intracranial aneurysm models.https://www.mdpi.com/2076-3425/12/5/603intracranial aneurysmaneurysmorgan on a chipaneurysm on a chipendothelial cellscomputational fluid dynamics
spellingShingle Aisen Vivas
Julia Mikhal
Gabriela M. Ong
Anna Eigenbrodt
Andries D. van der Meer
Rene Aquarius
Bernard J. Geurts
Hieronymus D. Boogaarts
Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
Brain Sciences
intracranial aneurysm
aneurysm
organ on a chip
aneurysm on a chip
endothelial cells
computational fluid dynamics
title Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
title_full Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
title_fullStr Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
title_full_unstemmed Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
title_short Aneurysm-on-a-Chip: Setting Flow Parameters for Microfluidic Endothelial Cultures Based on Computational Fluid Dynamics Modeling of Intracranial Aneurysms
title_sort aneurysm on a chip setting flow parameters for microfluidic endothelial cultures based on computational fluid dynamics modeling of intracranial aneurysms
topic intracranial aneurysm
aneurysm
organ on a chip
aneurysm on a chip
endothelial cells
computational fluid dynamics
url https://www.mdpi.com/2076-3425/12/5/603
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