A Review of Functional Analysis of Endothelial Cells in Flow Chambers

Abstract

The vascular endothelial cells constitute the innermost layer. The cells are exposed to mechanical stress by the flow, causing them to express their functions. To elucidate the functions, methods involving seeding endothelial cells as a layer in a chamber were studied. The chambers are known as parallel plate, T-chamber, step, cone plate, and stretch. The stimulated functions or signals from endothelial cells by flows are extensively connected to other outer layers of arteries or organs. The coculture layer was developed in a chamber to investigate the interaction between smooth muscle cells in the middle layer of the blood vessel wall in vascular physiology and pathology. Additionally, the microfabrication technology used to create a chamber for a microfluidic device involves both mechanical and chemical stimulation of cells to show their dynamics in in vivo microenvironments. The purpose of this study is to summarize the blood flow (flow inducing) for the functions connecting to endothelial cells and blood vessels, and to find directions for future chamber and device developments for further understanding and application of vascular functions. The relationship between chamber design flow, cell layers, and microfluidics was studied.

Integration of immune cells in organs-on-chips: a tutorial

“…Arterial BECs experience high shear stress, while venous BECs generally experience low shear stress. In vitro , shear stress can be applied in microfluidic systems, causing BECs to align along the flow direction and increase barrier tightness ( Ohta et al, 2022 ). When applying alternating flow, this BEC alignment is not observed, indicating that this method of applying shear stress is non-physiological ( Lee et al, 2019 ).…”

Endothelial mechanobiology under controlled disturbed flows

“…These include naturally occurring or surgical interventions in animal models, vertical step flow chambers, modified cone-plate viscometers, and microfluidic systems to elucidate the phenotypic adaptation of cells to flow. [17][18][19][20] Animal models for atherosclerosis often involve partial ligation of arteries that alter flows and cause changes incellular behaviors from atheroprotective to atheroprone in ligated regions. 26 Developing therapeutics to manage and mitigate vascular disease is a continuing exercise due to the high costs for animal studies in screening novel compounds.…”

“…16 Devices based on microscale technologies mainly use laminar unidirectional or oscillatory flows in straight microfluidic channels to assess changes in endothelial mechanobiology. 11,[17][18][19][20][21] Generating controlled disturbed flows, similar to those found in disease prone arterial regions, is an ongoing challenge to implement in lab-on-chip devices. 22 Whereas steady laminar channel flow past a ridge/ obstruction produces a separated flow in the wake, no secondary flows are generated.…”

Microfluidic platform for the reproduction of hypoxic vascular microenvironments

“…The blood vessel lumen is covered with a monolayer of vascular endothelial cells (ECs), which are deeply involved in the process of exchanging nutrients and waste products between blood and tissues. ECs are continuously exposed to mechanical stimuli caused by blood flow 1 , such as fluid shear stress of up to several Pa, and change their morphology and characteristics to maintain vascular function 2 . For instance, ECs orientate and elongate in the blood flow direction, sensing the fluid shear stress 3 and assembling actin stress fibers, which increases their mechanical stiffness 4 .…”