scholarly journals Endothelial cell polarization and orientation to flow in a novel microfluidic multimodal shear stress generator

Lab on a Chip ◽  
2020 ◽  
Vol 20 (23) ◽  
pp. 4373-4390
Author(s):  
Utku M. Sonmez ◽  
Ya-Wen Cheng ◽  
Simon C. Watkins ◽  
Beth L. Roman ◽  
Lance A. Davidson
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Microfluidic Device ◽  
Cell Polarization ◽  
Orientation Analysis ◽  
Stress Gradients ◽  
Multiple Levels

Endothelial cell polarization and orientation analysis using a novel microfluidic device that can simultaneously generate multiple levels of shear stress and shear stress gradients for systematic mechanobiology studies under flow.

Effects of Steady Spatial Wall Shear Stress Gradients on Endothelial Cell Morphology in Three-Dimensional Models

2007 ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Cell Morphology ◽  
Flow Direction ◽  
Stress Gradient ◽  
Spatial Gradient ◽  
Stress Gradients ◽  
Wall Shear

Endothelial cell (EC) dysfunction has been linked to atherosclerosis through their response to hemodynamic forces. Flow in stenotic vessels creates complex spatial gradients in wall shear stress. In vitro studies examining the effect of shear stress on endothelial cells have used unrealistic and simplified models, which cannot reproduce physiological conditions. The objective of this study was to expose endothelial cells to the complex shear shear pattern created by an asymmetric stenosis. Endothelial cells were grown and exposed for different times to physiological steady flow in straight dynamic controls and in idealized asymmetric stenosis models. Cells subjected to 1D flow aligned with flow direction and had a spindle-like shape when compared to static controls. Endothelial cell morphology was noticeable different in the regions with a spatial gradient in wall shear stress, being more randomly oriented and of cobblestone shape. This occurred despite the presence of an increased magnitude in shear stress. No other study to date has described this morphology in the presence of a positive wall shear stress gradient or gradient of significant shear magnitude. This technique provides a more realistic model to study endothelial cell response to spatial and temporal shear stress gradients that are present in vivo and is an important advancement towards a better understanding of the mechanisms involved in coronary artery disease.

Endothelial Cell Morphologic Response to Asymmetric Stenosis Hemodynamics: Effects of Spatial Wall Shear Stress Gradients

2010 ◽  
Vol 132 (8) ◽  
Author(s):  
Leonie Rouleau ◽  
Monica Farcas ◽  
Jean-Claude Tardif ◽  
Rosaire Mongrain ◽  
Richard L. Leask
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Wall Shear Stress ◽  
Atherosclerotic Plaque ◽  
Morphological Changes ◽  
Stress Gradients ◽  
Spatial Gradients ◽  
Wall Shear

Endothelial cells are known to respond to hemodynamic forces. Their phenotype has been suggested to differ between atheroprone and atheroprotective regions of the vasculature, which are characterized by the local hemodynamic environment. Once an atherosclerotic plaque has formed in a vessel, the obstruction creates complex spatial gradients in wall shear stress. Endothelial cell response to wall shear stress may be linked to the stability of coronary plaques. Unfortunately, in vitro studies of the endothelial cell involvement in plaque stability have been limited by unrealistic and simplified geometries, which cannot reproduce accurately the hemodynamics created by a coronary stenosis. Hence, in an attempt to better replicate the spatial wall shear stress gradient patterns in an atherosclerotic region, a three dimensional asymmetric stenosis model was created. Human abdominal aortic endothelial cells were exposed to steady flow (Re=50, 100, and 200 and τ=4.5 dyn/cm2, 9 dyn/cm2, and 18 dyn/cm2) in idealized 50% asymmetric stenosis and straight/tubular in vitro models. Local morphological changes that occur due to magnitude, duration, and spatial gradients were quantified to identify differences in cell response. In the one dimensional flow regions, where flow is fully developed and uniform wall shear stress is observed, cells aligned in flow direction and had a spindlelike shape when compared with static controls. Morphological changes were progressive and a function of time and magnitude in these regions. Cells were more randomly oriented and had a more cobblestone shape in regions of spatial wall shear stress gradients. These regions were present, both proximal and distal, at the stenosis and on the wall opposite to the stenosis. The response of endothelial cells to spatial wall shear stress gradients both in regions of acceleration and deceleration and without flow recirculation has not been previously reported. This study shows the dependence of endothelial cell morphology on spatial wall shear stress gradients and demonstrates that care must be taken to account for altered phenotype due to geometric features. These results may help explain plaque stability, as cells in shoulder regions near an atherosclerotic plaque had a cobblestone morphology indicating that they may be more permeable to subendothelial transport and express prothrombotic factors, which would increase the risk of atherothrombosis.

Bubble Motion in a Blood Vessel: Shear Stress Induced Endothelial Cell Injury

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
K. Mukundakrishnan ◽  
P. S. Ayyaswamy ◽  
D. M. Eckmann
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Bubble Dynamics ◽  
Cell Injury ◽  
Numerical Solutions ◽  
Multiple Scales ◽  
Membrane Integrity ◽  
Cell Membrane Integrity ◽  
Stress Gradients ◽  
Stress Variations

Mechanisms governing endothelial cell (EC) injury during arterial gas embolism have been investigated. Such mechanisms involve multiple scales. We have numerically investigated the macroscale flow dynamics due to the motion of a nearly occluding finite-sized air bubble in blood vessels of various sizes. Non-Newtonian behavior due to both the shear-thinning rheology of the blood and the Fahraeus–Lindqvist effect has been considered. The occluding bubble dynamics lends itself for an axisymmetric treatment. The numerical solutions have revealed several hydrodynamic features in the vicinity of the bubble. Large temporal and spatial shear stress gradients occur on the EC surface. The stress variations manifest in the form of a traveling wave. The gradients are accompanied by rapid sign changes. These features are ascribable to the development of a region of recirculation (vortex ring) in the proximity of the bubble. The shear stress gradients together with sign reversals may partially act as potential causes in the disruption of endothelial cell membrane integrity and functionality.

Endothelial cell polarization and chemotaxis in a microfluidic device

Lab on a Chip ◽  
2008 ◽  
Vol 8 (8) ◽  
pp. 1292 ◽  
Author(s):  
Amir Shamloo ◽  
Ning Ma ◽  
Mu-ming Poo ◽  
Lydia L. Sohn ◽  
Sarah C. Heilshorn
Keyword(s):  
Endothelial Cell ◽  
Microfluidic Device ◽  
Cell Polarization

Development of the Microfluidic Device to Regulate Shear Stress Gradients

2018 ◽  
Vol 12 (4) ◽  
pp. 294-303 ◽  
Author(s):  
Tae Hyeon Kim ◽  
Jong Min Lee ◽  
Christian D. Ahrberg ◽  
Bong Geun Chung
Keyword(s):  
Shear Stress ◽  
Microfluidic Device ◽  
Stress Gradients

scholarly journals Thrombin-Induced Endothelial Cell Damage Is Mitigated By Human Anti-Thrombin III in a Microfluidic Device

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 24-25
Author(s):  
William Wulftange ◽  
Erdem Kucukal ◽  
Yuncheng Man ◽  
Ran An ◽  
Karamoja Monchamp ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Microfluidic Device ◽  
Research Funding ◽  
Umbilical Vein ◽  
Coagulation Cascade ◽  
Human Umbilical Vein ◽  
At Iii ◽  
Umbilical Vein Endothelial Cells

Introduction Sickle cell disease (SCD) is a pleiotropic disease that results in a hypercoagulable state due to the depletion of natural anticoagulants and abnormal activation of the coagulation cascade. Vascular inflammation is a characteristic of SCD and can lead to endothelial cell activation and abnormally enhanced adhesion of hematopoietic cells. These adhesive events can lead to vaso-occlusive crises and are thus a target of pharmaceutical exploration. The complex pathophysiology of SCD suggests that there are many potential therapeutic targets, particularly during activation of the coagulation cascade. Presently, we describe the use of a microfluidic device to investigate the effectiveness of anti-thrombin III (AT-III) in mitigating thrombin-mediated effects on and red blood cell adhesion (RBC) to endothelial cells. Our microfluidic device, endothelium-on-a-chip (Fig. 1A), incorporates microchannels functionalized with endothelial cells (ECs), which allows for investigation of SCD pathophysiology under physiological shear stress. Here, we examine the extent to which thrombin causes cellular contraction in human umbilical vein endothelial cells (HUVECs) and the capacity of AT-III to mitigate this contraction. Similarly, we quantify the adhesion of sickle RBCs to thrombin-activated HUVECs and the adhesion to HUVECs pre-treated with AT-III. Methods Microchannels seeded with human umbilical vein endothelial cells (HUVECs) were cultured to confluency under flow for 48 - 72 hrs at 37 °C in a 5% CO2 atmosphere. Culture media containing 10% fetal bovine serum (FBS) was perfused through the microchannels at a shear stress of 1 dyne/cm2 which corresponds to a typical value seen in human post-capillary venules. Approximately 18 hours prior to the start of the experiment, perfused media was exchanged for ITS+1 media in order to condition cells to a low-serum environment and to avoid neutralization of thrombin by residual serum factors. At the start of each experiment, devices were disconnected from the dynamic flow culturing system and incubated with experimental reagents under static conditions. Endothelialized microchannels were treated with one of three conditions: Control channels were incubated with ITS+1 media for 5 hrs; Thrombin channels were incubated with ITS+1 media for 1 hr, followed by 5 IU/mL human alpha thrombin for 4 hrs; Anti-thrombin III channels were incubated with 7 IU/mL human anti-thrombin III (AT-III) for 1 hr, followed by 5 IU/mL human alpha thrombin for 4 hrs. AT-III was donated by Grifols USA (Los Angeles, California). Following each experiment, the endothelialized microchannels were fixed with 3.7% formalin. Microchannels were then imaged and confluency was measured using the FIJI plug-in PHANTAST with default settings. For adhesion experiments, whole blood samples were collected from 6 patients with homozygous SCD (HbSS). RBCs were isolated and suspended at 20% hematocrit in basal media, then perfused through treated, endothelialized microchannels. Microchannels were then imaged and adherent RBCs were quantified. Results The results of contraction and adhesion experiments are shown in Figures 1B&C, respectively. Control channels had an average confluency of 97.9% ± 1.7 (Fig. 1B&D), while thrombin-treated channels resulted in HUVEC contraction causing an average confluency of 63.7% ± 8.9 (Fig. 1B&E). Microchannels treated with AT-III prior to thrombin incubation had an average confluency of 92.5% ± 5.3 (Fig. 1B&F). Adhesion of sickled RBCs followed a similar trend: control channels had an average of 16.0 ± 22.7 RBCs per analyzed region (Fig. 1C&G), thrombin channels had an average of 222.8 ± 86.7 RBCs per analyzed region (Fig. 1C&H), and AT-III channels had an average of 19.6 ± 12.3 RBCs per analyzed region (Fig. 1C&I). Discussion We observed that thrombin treatment resulted in significant endothelial cell contraction. This thrombin induced cell contraction could be mitigated by pre-treating the microchannels with AT-III. Similarly, RBC adhesion significantly increased in thrombin-treated microchannels, and could be similarly mitigated by pre-treatment of the endothelium with AT-III. Taken together, our in vitro model suggests that AT-III may be worthy of investigation as a treatment for SCD associated thromboinflammation and vaso-occlusive crises. Disclosures An: Hemex Health, Inc.: Patents & Royalties. Little:NHLBI: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; GBT: Research Funding; Bluebird Bio: Research Funding; BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties). Key:Novo Nordisk: Other: Chair of Grants Committee; Takeda: Research Funding; Grifols: Research Funding; Uniqure: Consultancy. Gurkan:Hemex Health, Inc.: Consultancy, Current Employment, Patents & Royalties, Research Funding; BioChip Labs: Patents & Royalties; Dx Now Inc.: Patents & Royalties; Xatek Inc.: Patents & Royalties.

Naturally Produced Extracellular Matrix Is an Excellent Substrate for Canine Endothelial Cell Proliferation and Resistance to Shear Stress on PTFE Vascular Grafts

1997 ◽  
Vol 78 (05) ◽  
pp. 1392-1398 ◽  
Author(s):  
A Schneider ◽  
M Chandra ◽  
G Lazarovici ◽  
I Vlodavsky ◽  
G Merin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Cell Attachment ◽  
Thrombus Formation ◽  
Endothelial Cell Proliferation ◽  
Ptfe Graft ◽  
Vascular Prostheses ◽  
Endothelial Cell Attachment

SummaryPurpose: Successful development of a vascular prosthesis lined with endothelial cells (EC) may depend on the ability of the attached cells to resist shear forces after implantation. The present study was designed to investigate EC detachment from extracellular matrix (ECM) precoated vascular prostheses, caused by shear stress in vitro and to test the performance of these grafts in vivo. Methods: Bovine aortic endothelial cells were seeded inside untreated polytetrafluoro-ethylene (PTFE) vascular graft (10 X 0.6 cm), PTFE graft precoated with fibronectin (FN), or PTFE precoated with FN and a naturally produced ECM (106 cells/graft). Sixteen hours after seeding the medium was replaced and unattached cells counted. The strength of endothelial cell attachment was evaluated by subjecting the grafts to a physiologic shear stress of 15 dynes/cm2 for 1 h. The detached cells were collected and quantitated. PTFE or EC preseeded ECM coated grafts were implanted in the common carotid arteries of dogs. Results: While little or no differences were found in the extent of endothelial cell attachment to the various grafts (79%, 87% and 94% of the cells attached to PTFE, FN precoated PTFE, or FN+ECM precoated PTFE, respectively), the number of cells retained after a shear stress was significanly increased on ECM coated PTFE (20%, 54% and 85% on PTFE, FN coated PTFE, and FN+ECM coated PTFE, respectively, p <0.01). Implantation experiments in dogs revealed a significant increase in EC coverage and a reduced incidence of thrombus formation on ECM coated grafts that were seeded with autologous saphenous vein endothelial cells prior to implantation. Conclusion: ECM coating significantly increased the strength of endothelial cell attachment to vascular prostheses subjected to shear stress. The presence of adhesive macromolecules and potent endothelial cell growth promoting factors may render the ECM a promising substrate for vascular prostheses.

scholarly journals Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro.

1986 ◽  
Vol 83 (7) ◽  
pp. 2114-2117 ◽  
Author(s):  
P. F. Davies ◽  
A. Remuzzi ◽  
E. J. Gordon ◽  
C. F. Dewey ◽  
M. A. Gimbrone
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Cell Turnover ◽  
Fluid Shear ◽  
Turbulent Fluid

Effect of Shear Stress on Platelet Adhesion to Expanded Polytetrafluoroethylene, a Silicone Sheet, and an Endothelial Cell Monolayer

ASAIO Journal ◽  
2000 ◽  
Vol 46 (6) ◽  
pp. 696-701 ◽  
Author(s):  
Katsuko Sakai Furukawa ◽  
Takashi Ushida ◽  
Hirohito Sugano ◽  
Tamotsu Tamaki ◽  
Norio Ohshima ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Platelet Adhesion ◽  
Cell Monolayer ◽  
Endothelial Cell Monolayer ◽  
Expanded Polytetrafluoroethylene ◽  
Silicone Sheet

Shear stress regulates endothelial cell function through SRB1-eNOS signaling pathway

2016 ◽  
Vol 34 (5) ◽  
pp. 308-313 ◽  
Author(s):  
Ying Zhang ◽  
Bin Liao ◽  
Miaoling Li ◽  
Min Cheng ◽  
Yong Fu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Signaling Pathway ◽  
Cell Function ◽  
Endothelial Cell Function
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