Effect of shear stress on the proximal tubule-on-a-chip for multi-organ microphysiological system

Kim, Hyoungseob; Lee, Ju-Bi; Kim, Kyung‐Hee; Sung, Gun Yong

doi:10.1016/j.jiec.2022.08.010

Cited by 10 publications

(6 citation statements)

References 29 publications

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“…Many organ-on-chip models of the renal proximal tubule aim to create a perfused tubule lined with RPTEC by using various device designs where a hollow tubule is created using a gel substrate (Weber et al, 2016;Wilmer et al, 2016;Vormann et al, 2018;Lin et al, 2019;Ross et al, 2021). An alternative is to introduce media movement into a membrane-based system where RPTEC are seeded on the side of the membrane where lateral flow is introduced (Gao et al, 2011;Jang et al, 2013;Kim et al, 2022;Shaughnessey et al, 2022;Specioso et al, 2022). Indeed, most advanced 3D cultures of RPTEC focus on enabling shear stress in either membrane-based, or in-gel tubule microfluidic designs.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have examined fluidic membrane models similar in design to the PhysioMimix™ T12 plate used herein, with (Lee et al, 2022) and (Kim et al, 2022) utilizing custom injection-molded polycarbonate chips housing fluidic transwell membranes. Their studies utilized primary RPTECs cultured on either the upper (Lee et al, 2022) or lower (Kim et al, 2022) surfaces of the membranes. In their model, fluid flow (0.13 dyne/cm 2 ) was only present in the lower chamber, exposing cells on the lower side to fluid shear stress.…”

Section: Discussionmentioning

confidence: 99%

“…When static and fluidic conditions were compared (Lee et al, 2022), RPTECs exhibited comparable viability, glucose reabsorption, and transporter gene expression to controls. A subsequent study (Kim et al, 2022) showed that relocating RPTECs to the lower (fluidic) side of the membrane improved TEER, glucose reabsorption, and reduced permeability, emphasizing the need to position RPTECs 34 balance between mimicking physiological shear stress and maintaining cellular viability and function. In this respect, we acknowledge several limitations to our study.…”

Section: Discussionmentioning

confidence: 99%

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Comparative Analysis of the Physiological and Transport Functions of Various Sources of Renal Proximal Tubule Cells Under Static and Fluidic Conditions in PhysioMimix{trade mark, serif} T12 Platform

Sakolish,

Moyer,

Tsai

et al. 2024

Drug Metab Dispos

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In vitro models that can faithfully replicate critical aspects of kidney tubule function such as directional drug transport are in high demand in pharmacology and toxicology. Accordingly, development and validation of new models is underway. The objective of this study was to characterize physiological and transport functions of various sources of human renal proximal tubule epithelial cells (RPTECs). We tested TERT1-immortalized RPTEC, including OAT1-, OCT2-or OAT3-overexpressing variants, and primary RPTECs. Cells were cultured on transwell membranes in static (24-well transwells) and fluidic (transwells in PhysioMimix™ T12 organ-onchip with 2 L/s flow) conditions. Barrier formation, transport, and gene expression were evaluated. We show that two commercially available primary RPTECs were not suitable for studies of directional transport on transwells because they formed a substandard barrier even though they exhibited higher expression of transporters, especially under flow. TERT1-parent, -OAT1 and -OAT3 cells formed robust barriers, but were unaffected by flow. TERT1-OAT1 cells exhibited inhibitable para-aminohippurate transport, it was enhanced by flow. However, efficient tenofovir secretion and perfluorooctanoic acid reabsorption by TERT1-OAT1 cells were not modulated by flow. Gene expression showed that TERT1 and TERT1-OAT1 cells were most correlated with human kidney than other cell lines, but that flow did not have noticeable effects.Overall, our data show that addition of flow to in vitro studies of the renal proximal tubule may afford benefits in some aspects of modeling kidney function, but that careful consideration of the impact such adaptations would have on the cost and throughput of the experiments is needed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Analysis of the Physiological and Transport Functions of Various Sources of Renal Proximal Tubule Cells Under Static and Fluidic Conditions in PhysioMimix{trade mark, serif} T12 Platform

Sakolish,

Moyer,

Tsai

et al. 2024

Drug Metab Dispos

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“…Therefore, OoC platforms can substitute for two-dimensional cell culture and animal models due to ethical concerns and insufficient reproduction of human pathophysiology [ 351 ]. During the recent decade, OoC systems have been extensively utilized to replicate physiological microenvironment of several organs such as the gut [ 352 , 353 , 354 ], heart [ 355 , 356 , 357 ], liver [ 358 , 359 , 360 ], bone [ 361 , 362 , 363 ], kidney [ 364 , 365 , 366 ], lung [ 367 , 368 , 369 ] and brain [ 370 , 371 , 372 ]. In this section, current OoC studies based on the gut, bone, liver, brain, heart, kidney, and lung will be discussed.…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Biomedical Applications of Microfluidic Devices: A Review

et al. 2022

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Both passive and active microfluidic chips are used in many biomedical and chemical applications to support fluid mixing, particle manipulations, and signal detection. Passive microfluidic devices are geometry-dependent, and their uses are rather limited. Active microfluidic devices include sensors or detectors that transduce chemical, biological, and physical changes into electrical or optical signals. Also, they are transduction devices that detect biological and chemical changes in biomedical applications, and they are highly versatile microfluidic tools for disease diagnosis and organ modeling. This review provides a comprehensive overview of the significant advances that have been made in the development of microfluidics devices. We will discuss the function of microfluidic devices as micromixers or as sorters of cells and substances (e.g., microfiltration, flow or displacement, and trapping). Microfluidic devices are fabricated using a range of techniques, including molding, etching, three-dimensional printing, and nanofabrication. Their broad utility lies in the detection of diagnostic biomarkers and organ-on-chip approaches that permit disease modeling in cancer, as well as uses in neurological, cardiovascular, hepatic, and pulmonary diseases. Biosensor applications allow for point-of-care testing, using assays based on enzymes, nanozymes, antibodies, or nucleic acids (DNA or RNA). An anticipated development in the field includes the optimization of techniques for the fabrication of microfluidic devices using biocompatible materials. These developments will increase biomedical versatility, reduce diagnostic costs, and accelerate diagnosis time of microfluidics technology.

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“…63 Many studies have been conducted on various organs, such as organ-on-a-chip or organoid-on-a-chip, which represent the core of this system; however, research on hair follicle chips is very limited. [64][65][66][67][68][69][70][71][72][73][74][75] The lack of understanding of hair follicle formation and hair growth, and relatively low medical urgency compared with other organs may be the cause.…”

Section: H a I R -O N -A -C H I Pmentioning

confidence: 99%

Skin‐on‐a‐chip strategies for human hair follicle regeneration

Jeong

Nam

et al. 2022

Experimental Dermatology

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The number of hair loss patients increases every year, and hair loss treatment has several limitations, so research on hair is attracting attention recently. However, most current hair follicle research models are limited by their inability to replicate several key functions of the hair follicle microenvironment. To complement this, an in vitro culture system similar to the in vivo environment must be constructed. It is necessary to develop a hair-on-a-chip that implements a fully functional hair follicle model by reproducing the main characteristics of hair follicle morphogenesis and cycle. In this review, we summarize the gradation of hair follicle morphogenesis and the roles and mechanisms of molecular signals involved in the hair follicle cycle. In addition, we discuss research results of various in vitro organoid products and organ-on-achip-based hair follicle tissue chips for the treatment of alopecia and present future research and development directions.

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Effect of shear stress on the proximal tubule-on-a-chip for multi-organ microphysiological system

Cited by 10 publications

References 29 publications

Comparative Analysis of the Physiological and Transport Functions of Various Sources of Renal Proximal Tubule Cells Under Static and Fluidic Conditions in PhysioMimix{trade mark, serif} T12 Platform

Comparative Analysis of the Physiological and Transport Functions of Various Sources of Renal Proximal Tubule Cells Under Static and Fluidic Conditions in PhysioMimix{trade mark, serif} T12 Platform

Biomedical Applications of Microfluidic Devices: A Review

Skin‐on‐a‐chip strategies for human hair follicle regeneration

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