Flow stimulates drug transport in a human kidney proximal tubule-on-a-chip independent of primary cilia

Vriend, Jelle; Peters, Janny G. P.; Nieskens, Tom T.G.; Škovroňová, Renata; Blaimschein, Nina; Schmidts, Miriam; Roepman, Ronald; Schirris, Tom J.J.; Rüssel, Frans G. M.; Masereeuw, Rosalinde; Wilmer, Martijn J.

doi:10.1016/j.bbagen.2019.129433

Cited by 61 publications

(49 citation statements)

References 43 publications

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“…Differently from static culture systems, a fundamental advance in tubule-on-a-chip technology was the microfluidic device that provided a mechanical stimulus, the fluid shear stress (FSS), that affects the cellular structure and the expression of proteins linked to specific tubular functions [122][123][124]. More importantly, the generation of leak-tight, polarized kidney tubules enabled to recapitulate physiological (trans-epithelial) activity including cellular uptake of albumin [120,121,125], secretory clearance of albumin-bound uremic toxins [61], transportation of sodium/ potassium, urea, creatinine, glucose and bicarbonate, and vitamin D activation [115].…”

Section: Tubule-on-a-chipmentioning

confidence: 99%

Bioengineering strategies for nephrologists: kidney was not built in a day

Peired

Mazzinghi

Chiara

et al. 2020

Expert Opinion on Biological Therapy

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Introduction: The number of patients with end-stage kidney disease is increasing worldwide, creating an unprecedented organ shortage. The kidney is a highly complex structure performing many crucial functions. Dialysis replaces filtration but not all other kidney functions and transplant is limited by kidney availability. Numerous innovative ways are being explored to obtain new kidneys for disease modeling and potentially replace lost kidney functions. Areas covered: In this review, we will go through the different approaches that have been developed over the years to build kidneys. We will first present the current advances in xenotransplantation and generation of interspecies chimeras. Next, we will examine the attempts to create bioengineered kidneys with hemodialysis-derived implantable devices and decellularized organs. Finally, we will examine how organoids and microfluidic devices could answer important pathophysiological questions and model the path toward creating in vitro functional organs, for example through 3D bioprinting. Expert opinion: While all the aforementioned approaches to create new kidneys are promising, their translation into clinical practice seems a long way off, except xenotransplantation. Nonetheless, these novel technologies already consent disease modeling and drug testing at 3D level. We will review the stages of progress toward patient therapy and advantages/drawbacks of the various strategies.

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Section: Tubule-on-a-chipmentioning

confidence: 99%

Bioengineering strategies for nephrologists: kidney was not built in a day

Peired

Mazzinghi

Chiara

et al. 2020

Expert Opinion on Biological Therapy

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“…Literature analysis points toward a cell-type specific integration capability for physical and chemical signals, tightly related to the functional ancestry of the original tissue. In addition to endothelial cells, shear stress stimulation can be of relevance for the physiological function of many organ systems like for instance the gastrointestinal tract [124][125][126] or the kidneys [3,9,10,127,128]. In general, combinatory studies report an amplification of the biological response compared to static conditions.…”

Section: Non-endothelial Cellsmentioning

confidence: 99%

“…This approach allowed to identify differential toxicity of gentamycin given in a single bolus or a chronic regime [139]. Moreover, flow conditions (2-0.5 dyn/cm 2 ) modulate the cytotoxicity of cyclosporine A (30 µM) in proximal tubule epithelial cells (PTECs) [128]. For human lung adenocarcinoma cell line, A549 and pancreatic adenocarcinoma cells PANC-1 shear stress induced no toxicity per se (0.5 dyn/cm 2 ), but enhanced the cytotoxic potential of doxorubicin (1 µg/mL, MTT assay) [137].…”

Section: Non-endothelial Cellsmentioning

confidence: 99%

“…In the excretory function, kidney epithelial cells are constantly challenged by shear stress and substrate deformation [217]. Hence, biomechanical cues exert profound impact on their physiological regulation and cells can tune the activity of efflux pumps and transport mechanisms in response to shear stress [128,218]. In addition, renal proximal tubule epithelial cells increase the expression of tight-junctions in response to substrate topology and shear stress [219].…”

Section: Excretionmentioning

confidence: 99%

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Integrating Biophysics in Toxicology

Favero

Kraegeloh

2020

Cells

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Integration of biophysical stimulation in test systems is established in diverse branches of biomedical sciences including toxicology. This is largely motivated by the need to create novel experimental setups capable of reproducing more closely in vivo physiological conditions. Indeed, we face the need to increase predictive power and experimental output, albeit reducing the use of animals in toxicity testing. In vivo, mechanical stimulation is essential for cellular homeostasis. In vitro, diverse strategies can be used to model this crucial component. The compliance of the extracellular matrix can be tuned by modifying the stiffness or through the deformation of substrates hosting the cells via static or dynamic strain. Moreover, cells can be cultivated under shear stress deriving from the movement of the extracellular fluids. In turn, introduction of physical cues in the cell culture environment modulates differentiation, functional properties, and metabolic competence, thus influencing cellular capability to cope with toxic insults. This review summarizes the state of the art of integration of biophysical stimuli in model systems for toxicity testing, discusses future challenges, and provides perspectives for the further advancement of in vitro cytotoxicity studies.

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“…The materials used to construct the device, as well as the dimensions of the different components, vary depending on study design. In addition to the multitude of devices developed in research labs, commercial platforms are available including the OrganoPlate 35 , 44 , 49 , 50 (Mimetas, Netherlands) and the Kidney-Chip 22 (Emulate, US).…”

Section: Mimicking Kidney Tubules For Applications To Sars-cov-2mentioning

confidence: 99%

Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection

Ryan

Simmons

2020

Cel. Mol. Bioeng.

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The kidneys are susceptible to adverse effects from many diseases, including several that are not tissue-specific. Acute kidney injury is a common complication of systemic diseases such as diabetes, lupus, and certain infections including the novel coronavirus (SARS-CoV-2). Microfluidic devices are an attractive option for disease modeling, offering the opportunity to utilize human cells, control experimental and environmental conditions, and combine with other on-chip devices. For researchers with expertise in microfluidics, this brief perspective highlights potential applications of such devices to studying SARS-CoV-2-induced kidney injury.

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Flow stimulates drug transport in a human kidney proximal tubule-on-a-chip independent of primary cilia

Cited by 61 publications

References 43 publications

Bioengineering strategies for nephrologists: kidney was not built in a day

Bioengineering strategies for nephrologists: kidney was not built in a day

Integrating Biophysics in Toxicology

Potential Applications of Microfluidics to Acute Kidney Injury Associated with Viral Infection

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