A human proximal tubule-on-a-chip to study renal disease and toxicity

Sakolish, Courtney; Philip, Brian; Mahler, Gretchen J.

doi:10.1063/1.5083138

Cited by 48 publications

(53 citation statements)

References 51 publications

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“…The chip was applicable for nephrotoxicity assessments, therapeutic development, regenerative medicine, and kidney development and disease. Sakolish et al [77] produced a reusable microfluidic chip in human proximal tubules and glomeruli that permitted renal epithelial cells to grow under various conditions. Shear stress causes nephrotoxicity.…”

Section: Kidney Ooacmentioning

confidence: 99%

Organ-on-a-chip: recent breakthroughs and future prospects

et al. 2020

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BackgroundMicrofluidics is a science and technology that precisely manipulates and processes microscale fluids. It is commonly used to precisely control microfluidic (10 −9 to 10 −18 L) fluids using channels that range in size from tens to hundreds of microns and is known as a "lab-on-a-chip" [1][2][3][4]. The microchannel is small, but has a large surface area and high mass transfer, favoring its use in microfluidic technology applications including low regent usage, controllable volumes, fast mixing speeds, rapid responses, and precision control of physical and chemical properties [1,5,6]. Microfluidics integrate sample preparation, reactions, separation, detection, and basic operating units such as cell culture, sorting and cell lysis [7]. For these reasons, interest in OOAC has intensified [8]. OOAC combines a range of chemical, biological and material science disciplines [9] and was selected as one of the "Top Ten Emerging Technologies" in the World Economic Forum [10].OOAC is a biomimetic system that can mimic the environment of a physiological organ, with the ability to regulate key parameters including AbstractThe organ-on-a-chip (OOAC) is in the list of top 10 emerging technologies and refers to a physiological organ biomimetic system built on a microfluidic chip. Through a combination of cell biology, engineering, and biomaterial technology, the microenvironment of the chip simulates that of the organ in terms of tissue interfaces and mechanical stimulation. This reflects the structural and functional characteristics of human tissue and can predict response to an array of stimuli including drug responses and environmental effects. OOAC has broad applications in precision medicine and biological defense strategies. Here, we introduce the concepts of OOAC and review its application to the construction of physiological models, drug development, and toxicology from the perspective of different organs. We further discuss existing challenges and provide future perspectives for its application.

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Section: Kidney Ooacmentioning

confidence: 99%

Organ-on-a-chip: recent breakthroughs and future prospects

et al. 2020

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“…In addition to providing a shear-stressed culture environment for HK-2 cells, the platform contained a glomerular filter containing HUVECs to provide a more realistic "primary urine" inside the device. Later, the group used such a platform to evaluate the DIN by cisplatin and cyclosporine [82]. The results show that HK-2 cells cultured in this microfluidic device are more sensitive.…”

Section: Kidney-on-a-chip For Drug Nephrotoxicity Testingmentioning

confidence: 99%

“…The results show that HK-2 cells cultured in this microfluidic device are more sensitive. Musah et al demonstrated that fluid shear stress could promote the proximal tubular epithelial cells (PTECs) to retain more mature phenotypes and develop a glomerulus-on-a-chip model [82]. Weber and his team [83] combined the single-channel Norvatis microphysiology system (MPS) and the PTECs to reconstruct the physiological function of human proximal tubules in vitro and used this platform to evaluate the nephrotoxicity of polymyxin antibiotics.…”

Section: Kidney-on-a-chip For Drug Nephrotoxicity Testingmentioning

confidence: 99%

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

et al. 2020

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Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

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“…This technology was helpful to reproduce the in vivo cisplatin and gentamicin toxicity, demonstrating that the once-a-day bolus dosing method was less nephrotoxic than the continuous infusion method [137]. Moreover, the combination of tubule-on -a-chip systems with innovative detection methods to analyze novel biomarkers specific for nephrotoxicity identifies this technology as a fully compatible platform with automation and high content screening equipment [134][135][136][137][138][139][140][141]. However, the goal standard in understanding nephrotoxicity is the integration of multiple cell types from different organs.…”

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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A human proximal tubule-on-a-chip to study renal disease and toxicity

Cited by 48 publications

References 51 publications

Organ-on-a-chip: recent breakthroughs and future prospects

Organ-on-a-chip: recent breakthroughs and future prospects

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

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

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