P21-activated kinase regulates oxygen-dependent migration of vascular endothelial cells in monolayers

Hirose, Satomi; Tabata, Yasuhiko; Sone, Kazuki; Takahashi, Naoyuki; Yoshino, Daisuke; Funamoto, Kenichi

doi:10.1080/19336918.2021.1978368

Cited by 8 publications

(21 citation statements)

References 35 publications

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“…Experiments combined with micropatterning can also be conducted by modifying the surface properties of the substrate like hardness and hydrophilicity by coating with hydrogel or other materials [ 127 , 128 ] or by plasma treatment [ 8 ]. Furthermore, the effects of oxygen tension on ECs can be studied by manipulating the dissolved gas components in the cell culture medium [ 125 , 129 , 130 ]. As for a device structure, it has been proposed that a channel for culturing ECs and another separated channel be located sandwiching a membrane with nano-sized pores [ 131 , 132 , 133 ] or a hydrogel.…”

Section: Resultsmentioning

confidence: 99%

A Review of Functional Analysis of Endothelial Cells in Flow Chambers

Ohta

Sakamoto

Funamoto

et al. 2022

JFB

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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.

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Section: Resultsmentioning

confidence: 99%

A Review of Functional Analysis of Endothelial Cells in Flow Chambers

Ohta

Sakamoto

Funamoto

et al. 2022

JFB

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“…Observation of cell migration free from the geometrical constraint of the channel would be instructive. By replicating the experimental settings used in former experiments 29 , 30 , only the ECs on the bottom glass coverslip of the media channel were investigated. Investigations of the changes of cell behaviors and endothelial permeability at the interface between gel and media channels will be examined in the future work.…”

Section: Discussionmentioning

confidence: 99%

“…Collective migration and morphological changes of ECs formed a confluent monolayer on the bottom of the media channel were measured by controlling the oxygen concentration and media flow 29 , 30 . Human umbilical vein endothelial cells (HUVECs) (C2517A; Lonza, Switzerland) below the 9th passage were used in the experiment.…”

Section: Methodsmentioning

confidence: 99%

“…A confluent EC monolayer exposed to a hypoxic stress of around 3% O 2 exhibited increased permeability and lost a size-selective barrier function 31 . In addition, collective migration of ECs measured by particle image velocimetry (PIV) using a time-series of phase-contrast microscopic images revealed an oxygen-dependent variation in migration speed, which increased at around 3% O 2 but decreased at < 1% O 2 29 . Although our previous experiments on vascular endothelial responses to hypoxia were performed under a static condition without flow exposure for simplification, ECs in an in vivo vascular microenvironment are exposed to blood flows.…”

Section: Introductionmentioning

confidence: 99%

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Microfluidic platform for the reproduction of hypoxic vascular microenvironments

Takahashi

Yoshino

SUGAHARA

et al. 2023

Sci Rep

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Vascular endothelial cells (ECs) respond to mechanical stimuli caused by blood flow to maintain vascular homeostasis. Although the oxygen level in vascular microenvironment is lower than the atmospheric one, the cellular dynamics of ECs under hypoxic and flow exposure are not fully understood. Here, we describe a microfluidic platform for the reproduction hypoxic vascular microenvironments. Simultaneous application of hypoxic stress and fluid shear stress to the cultured cells was achieved by integrating a microfluidic device and a flow channel that adjusted the initial oxygen concentration in a cell culture medium. An EC monolayer was then formed on the media channel in the device, and the ECs were observed after exposure to hypoxic and flow conditions. The migration velocity of the ECs immediately increased after flow exposure, especially in the direction opposite to the flow direction, and gradually decreased, resulting in the lowest value under the hypoxic and flow exposure condition. The ECs after 6-h simultaneous exposure to hypoxic stress and fluid shear stress were generally aligned and elongated in the flow direction, with enhanced VE-cadherin expression and actin filament assembly. Thus, the developed microfluidic platform is useful for investigating the dynamics of ECs in vascular microenvironments.

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“…Various microfluidic devices have also been developed to control microenvironmental oxygen concentrations by chemical reactions with an oxygen scavenger, such as sodium sulfite [35,36], or by gas exchange by supplying gas mixtures at predefined oxygen concentrations [37,38]. Our group has developed microfluidic devices that enable the precise and rapid control of oxygen concentrations for the real-time observation of cells [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

The Oxygen Gradient in Hypoxic Conditions Enhances and Guides Dictyostelium discoideum Migration

et al. 2022

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Spatiotemporal variations of oxygen concentration affect the cell behaviors that are involved in physiological and pathological events. In our previous study with Dictyostelium discoideum (Dd) as a model of cell motility, aggregations of Dd cells exhibited long-lasting and highly stable migration in a self-generated hypoxic environment, forming a ring shape that spread toward the outer higher oxygen region. However, it is still unclear what kinds of changes in the migratory properties are responsible for the observed phenomena. Here, we investigated the migration of Dd to clarify the oxygen-dependent characteristics of aerokinesis and aerotaxis. Migratory behaviors of Dd cells were analyzed under various oxygen concentration gradients and uniform oxygen conditions generated in microfluidic devices. Under hypoxic conditions below 2% O2, corresponding to less than 25 µM O2 in the culture medium, the migration of Dd cells was enhanced (aerokinesis) and the oxygen gradient guided the cells toward the oxygen-rich region (aerotaxis). The aerotaxis was attributed to the increase in the frequency of migration associated with the direction of higher O2, the acceleration of migration velocity, and the enhancement of migration straightness. Thus, aerokinesis and aerotaxis are dependent on both the oxygen level and possibly relative gradient and are essential mechanisms for the migration of Dd.

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P21-activated kinase regulates oxygen-dependent migration of vascular endothelial cells in monolayers

Cited by 8 publications

References 35 publications

A Review of Functional Analysis of Endothelial Cells in Flow Chambers

A Review of Functional Analysis of Endothelial Cells in Flow Chambers

Microfluidic platform for the reproduction of hypoxic vascular microenvironments

The Oxygen Gradient in Hypoxic Conditions Enhances and Guides Dictyostelium discoideum Migration

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