Enhanced podocyte differentiation and changing drug toxicity sensitivity through pressure-controlled mechanical filtration stress on a glomerulus-on-a-chip

Doi, Kotaro; Kimurâ, Hiroshi; Kim, Soo Hyeon; Kaneda, Shohei; Wada, Takehiko; Tanaka, Tetsuhiro; Shimizu, Akira; Sano, Takanori; Chikamori, Masatomo; Shinohara, Masanao; Matsunaga, Yukiko T.; Nangaku, Masaomi; Fujii, Teruo

doi:10.1039/d2lc00941b

Cited by 8 publications

(8 citation statements)

References 68 publications

(106 reference statements)

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“…Porous membranes are typically coated with ECM such as collagen I or IV to promote podocyte adhesion. Studies have shown that utilizing different ECM compositions, particularly laminin 521, enhanced podocyte attachment and proliferation ( Doi et al, 2023 ). Optimal filtration flow rates also play a crucial role in facilitating podocyte monolayer formation.…”

Section: Functional Kidney Units-on-a-chipmentioning

confidence: 99%

“…In podocytes, F-actin and actin-associated protein synaptopodin decreased, and the expressions of slit diaphragm proteins nephrin and podocin also decreased. Doi K et al developed a glomerulus-on-a-chip that precisely regulated fluid flow and filtration pressure by controlling air pressure to explore the effects of filtration stimulation on podocyte differentiation ( Doi et al, 2023 ). Their results showed that filtration stimuli with a pressure of 0.10 kPa induced and maintained the foot processes of podocytes by upregulating the expression of synaptopodin, CD2-related proteins, and vascular endothelial growth factor-A, and could affect the response of podocytes to drugs.…”

Section: Functional Kidney Units-on-a-chipmentioning

confidence: 99%

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Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond

Huang,

Chen,

et al. 2024

Front. Bioeng. Biotechnol.

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Organs-on-a-chip (OoC) is a microengineered three-dimensional cell culture system developed for decades. Utilizing microfluidic technology, OoC cultivates cells on perfusable channels to construct in vitro organ models, enabling the simulation of organ-level functions under physiological and pathophysiological conditions. The superior simulation capabilities compared to traditional animal experiments and two-dimensional cell cultures, making OoC a valuable tool for in vitro research. Recently, the application of OoC has extended to the field of nephrology, where it replicates various functional units, including glomerulus-on-a-chip, proximal tubule-on-a-chip, distal tubule-on-a-chip, collecting duct-on-a-chip, and even the entire nephron-on-a-chip to precisely emulate the structure and function of nephrons. Moreover, researchers have integrated kidney models into multi-organ systems, establishing human body-on-a-chip platforms. In this review, the diverse functional kidney units-on-a-chip and their versatile applications are outlined, such as drug nephrotoxicity screening, renal development studies, and investigations into the pathophysiological mechanisms of kidney diseases. The inherent advantages and current limitations of these OoC models are also examined. Finally, the synergy of kidney-on-a-chip with other emerging biomedical technologies are explored, such as bioengineered kidney and bioprinting, and a new insight for chip-based renal replacement therapy in the future are prospected.

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Section: Functional Kidney Units-on-a-chipmentioning

confidence: 99%

Section: Functional Kidney Units-on-a-chipmentioning

confidence: 99%

Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond

Huang,

Chen,

et al. 2024

Front. Bioeng. Biotechnol.

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“…3 MPS have been proposed for various organs and tissues, including the liver, gut, kidney, and blood–brain barrier (BBB) to study their functions in relation to absorption, distribution, metabolism, and excretion, especially in the context of drug discovery. 2,4–9…”

Section: Introductionmentioning

confidence: 99%

Standalone cell culture microfluidic device-based microphysiological system for automated cell observation and application in nephrotoxicity tests

Kimura,

Nakamura,

Goto

et al. 2024

Lab Chip

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“…Therefore, many researchers are interested in studying defective digestive, immune, and endocrine functions as well as diseases such as infection, inflammation, and cancer using animal models. These models have been enormously challenged by unethical and costly issues caused by using different kinds of animals [ 27 , 28 , 29 , 30 , 31 ]. Therefore, a lab-on-a-chip was proposed as a solution to replace animal models with many unsolvable problems.…”

Section: Introductionmentioning

confidence: 99%

Bio–Microfabrication of 2D and 3D Biomimetic Gut-on-a-Chip

Jang,

Jung,

2023

Micromachines

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Traditional goal of microfabrication was to limitedly construct nano- and micro-geometries on silicon or quartz wafers using various semiconductor manufacturing technologies, such as photolithography, soft lithography, etching, deposition, and so on. However, recent integration with biotechnologies has led to a wide expansion of microfabrication. In particular, many researchers studying pharmacology and pathology are very interested in producing in vitro models that mimic the actual intestine to study the effectiveness of new drug testing and interactions between organs. Various bio–microfabrication techniques have been developed while solving inherent problems when developing in vitro micromodels that mimic the real large intestine. This intensive review introduces various bio–microfabrication techniques that have been used, until recently, to realize two-dimensional and three-dimensional biomimetic experimental models. Regarding the topic of gut chips, two major review subtopics and two-dimensional and three-dimensional gut chips were employed, focusing on the membrane-based manufacturing process for two-dimensional gut chips and the scaffold-based manufacturing process for three-dimensional gut chips, respectively.

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Enhanced podocyte differentiation and changing drug toxicity sensitivity through pressure-controlled mechanical filtration stress on a glomerulus-on-a-chip

Abstract: Podocytes, localized in the glomerulus, are a prognostic factor of proteinuria in kidney disease and are exposed to distinct physiological stimuli from basal to apical filtration flow. Research on drug...

Cited by 8 publications

References 68 publications

Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond

Revolutionizing nephrology research: expanding horizons with kidney-on-a-chip and beyond

Standalone cell culture microfluidic device-based microphysiological system for automated cell observation and application in nephrotoxicity tests

Bio–Microfabrication of 2D and 3D Biomimetic Gut-on-a-Chip

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