Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening

Wilmer, Martijn J.; Ng, Chee Ping; Lanz, Henriëtte L.; Vulto, Paul; Suter‐Dick, Laura; Masereeuw, Rosalinde

doi:10.1016/j.tibtech.2015.11.001

Cited by 303 publications

(221 citation statements)

References 102 publications

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“…Kidney-on-a-chip technology is being employed in the drug discovery field using in vitro models that mimic kidney physiologic structures and continuous flow conditions (74,80,81). Most systems consist of kidney tubular epithelial cells embedded on the surface of an extracellular matrix, which is attached to perfusable microchannels that allow for nutrient enrichment, waste clearance, and flow (81).…”

Section: Preclinical and Clinical Tests For Drug-induced Nephrotoxicitymentioning

confidence: 99%

“…Most systems consist of kidney tubular epithelial cells embedded on the surface of an extracellular matrix, which is attached to perfusable microchannels that allow for nutrient enrichment, waste clearance, and flow (81). These in vitro models, in particular the 3D models, are thought to more reliably replicate the in vivo environment and predict nephrotoxicity that occurs with certain drugs in the clinical setting (81). Proximal tubular cells cultured under these physiologic conditions demonstrate various markers of drug cytotoxicity.…”

Section: Preclinical and Clinical Tests For Drug-induced Nephrotoxicitymentioning

confidence: 99%

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Pharmacology behind Common Drug Nephrotoxicities

Perazella

2018

CJASN

174

154

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Patients are exposed to numerous prescribed and over-the-counter medications. Unfortunately, drugs remain a relatively common cause of acute and chronic kidney injury. A combination of factors including the innate nephrotoxicity of drugs, underlying patient characteristics that increase their risk for kidney injury, and the metabolism and pathway of excretion by the kidneys of the various agents administered enhance risk for druginduced nephrotoxicity. This paper will review these clinically relevant aspects of drug-induced nephrotoxicity for the clinical nephrologist.

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Section: Preclinical and Clinical Tests For Drug-induced Nephrotoxicitymentioning

confidence: 99%

Section: Preclinical and Clinical Tests For Drug-induced Nephrotoxicitymentioning

confidence: 99%

Pharmacology behind Common Drug Nephrotoxicities

Perazella

2018

CJASN

174

154

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“…8 Despite these early promising outcomes, the recapitulation of tissue functionalities by many constructs remains largely untested, and their predictive performance against current models remains to be validated. 9 A long-term goal is to incorporate organotypic cell cultures into precision medicine applications by using induced pluripotent stem cells to generate patient-and populationspecific organs-on-chips. 10 However, in vitro data do not directly emulate clinical observations, and several challenges remain in translating insight from in vitro systems to in vivo outcomes.…”

Section: What Is Systems Biology?mentioning

confidence: 99%

A Better, Faster Road From Biological Data to Human Health: A Systems Biology Approach for Engineered Cell Cultures

Hawkins¹,

Grego²

2017

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Key Issues and Opportunities• Because of the limitations of animal models and in vitro assays, the pipeline for new therapeutics grows smaller and chemical toxicity screening is failing to meet the growing demand for hazard assessment.• Engineered cellular constructs provide access to physiologically relevant in vitro data of sufficient quality for improved predictive modeling of human responses.• Sophisticated computational tools are needed to translate in vitro biological data to actionable information about health effects of bioactive compounds. Research Brief RTI Press June 2017Traditionally, the interactions of drugs and toxicants with human tissue have been investigated in a reductionist way-for example, by focusing on specific molecular targets and using single-cell-type cultures before testing compounds in whole organisms. More recently, systems biology approaches attempt to enhance the predictive value of in vitro biological data by adopting a comprehensive description of biological systems and using sophisticated computational tools that can deal with the complexity of these systems. However, the utility of computational models resulting from these efforts completely relies on the quality of the data used to construct them. Here, we propose that recent advances in the development of bioengineered, 3D, multicellular constructs provide in vitro data of sufficient complexity and physiological relevance to be used in predictive systems biology models of human responses. Such predictive models are essential to maximally leveraging these emerging bioengineering technologies to improve both therapeutic development and toxicity risk assessment.This brief outlines the opportunities presented by emerging technologies and approaches for the acceleration of drug development and toxicity testing, as well as the challenges lying ahead for the field. What Is Systems Biology?• The data-based, computational, and mathematical modeling of complex biological systems and their dynamic behavior• A paradigm in antithesis to reductionist approaches of biological response focused on "one gene, one receptor, one mechanism"• Driven by the advent of high-throughput bioassays and increased computational power that enable bioinformatics analysis of -omics data• Network-centric view, with focus on mathematical description of signaling, transcriptional, and metabolic networks and their interactions• Aims at discovering network-level properties not evident from the study of individual components (emergent properties)

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“…While many kidney-on-a-chip studies have been reported, most of them focused on the nephrotoxicity rather than renal excretion. 15 Previously, we developed a preliminary prototype of a microcirculation model, 16 which was composed of a pneumatic micro-peristaltic pump (heart), dialysis component using a dialysis membrane (renal corpuscle), and cell culture chamber (drug target) to mimic the excretion process. This model was, however, a preliminary proof-of-concept model with very low efficiency.…”

Section: Introductionmentioning

confidence: 99%

Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention

2017

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Here, we developed a multichannel dialysis microchip having three sets of dialysis systems, which consisted of three independent circulation channels with a common micropump. Each dialysis system was composed of a pneumatic micropump (heart), dialysis unit (renal corpuscle), and cell culture chamber (drug target) as well as circulation and dialysate channels to mimic the circulation system. Small molecules were successfully separated in parallel from macromolecules at the dialysis components. Anticancer tests using this microchip showed results that considered both serum protein-binding nature and drug activity. In the anticancer bioassay, the multichannel chip showed similar reproducible and reliable results as those of the single-channel system but with higher throughput.

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Kidney-on-a-Chip Technology for Drug-Induced Nephrotoxicity Screening

Cited by 303 publications

References 102 publications

Pharmacology behind Common Drug Nephrotoxicities

Pharmacology behind Common Drug Nephrotoxicities

A Better, Faster Road From Biological Data to Human Health: A Systems Biology Approach for Engineered Cell Cultures

Development of a Multichannel Dialysis Microchip for Bioassay of Drug Efficacy and Retention

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