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New scientific publication in collaboration with the University of Newcastle on modelling Stargardt disease (STGD1) in vitro with retinal organoids (RO) to unravel genotype-phenotype correlations

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Kidney Toxicity Service

Newcells kidney tissue models

Accelerate your lead compound selection by evaluating their safety in kidney tissue.

1.

Fully differentiated and polarised kidney proximal tubule cells

2.

Measurement of FDA-approved renal toxicity biomarkers

3.

High predictivity of in vivo and clinical outcomes

Predictive and investigative kidney toxicity and drug safety evaluation, in vitro

Drug-induced nephrotoxicity is one of the leading causes of drug failure as the prediction of kidney toxicity during new drug development remains inaccurate. Early detection of in vitro nephrotoxicity is key to reducing both costs and timelines of drug development. Nephrotoxicity assays, which evaluate kidney toxicity using human-relevant models, provide essential data and insights to improve drug safety. The FDA recommends in vitro nephrotoxicity assessment of new drugs and biologics prior to in vivo assessments in animal models. Newcells kidney in vitro nephrotoxicity assays allow researchers to better predict renal safety profiles earlier in the drug development process.

Additional regulatory guidance from both the FDA and EMA also recommends the detection of early markers of kidney toxicity such as KIM-1, NGAL and clusterin, which can only be quantified in more complex in vitro kidney microtissue models. Such models are therefore needed for reliable predictive and early evaluation of renal safety profiles. Newcells aProximate™ proximal tubule cell model is an advanced microtissue model containing all relevant biomarkers and is designed to asses renal toxicity with unparalleled accuracy. It enables detection of early and late toxic effects, fulfilling a critical need in the field of in vitro nephrotoxicity assessment, through detection of early nephrotoxic markers and transporter activity.

The BASIC Nephrotoxicity study rapidly assesses renal toxicity in human, mouse, rat or dog through quantification of cellular viability (ATP and LDH levels) and trans-epithelial electrical resistance (TEER).

The COMPREHENSIVE Nephrotoxicity study is an in-depth assessment of renal toxicity in human, mouse, rat or dog. This study also includes quantification of FDA-approved kidney injury markers NGAL, KIM1 and Clusterin, ensuring your IND submissions will be further strengthened by the testing of parameters and biomarkers that follow regulatory guidelines.

Gene analysis, inhibitor study and species comparison (human, mouse, rat and dog) are available as insightful complements.

Service outputs

  • Assessment of FDA-approved biomarkers of kidney toxicity: KIM-1, NGAL and clusterin
  • Cell viability: ATP, LDH and TEER measurements
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Full safety profile

Multiple species

96-well

Assays

  • BASIC Nephrotoxicity study (cell viability and TEER)
  • COMPREHENSIVE Nephrotoxicity study (cell viability, TEER, FDA injury markers assessment)

Models

  • aProximate™ kidney proximal tubule cells (from human, mouse, rat and dog)

Timeline

  • 2-3 months
Service overview Close Open

Our service provides insights into drug-induced nephrotoxicity

Newcells offers in vitro kidney toxicity evaluation by testing your compounds on aProximate™. Evaluation of proximal tubule Nephrotoxicity in vitro will assess the renal safety profiles of your compounds, significantly accelerating your drug safety studies.

The data generated from our renal toxicity assays provides a comprehensive understanding of the safety profile of your compounds by testing parameters which follow regulatory guidelines, giving you confidence in your lead candidates ahead of further in vivo animal testing.

aProximate™ allows the assessment of nephrotoxicity across a range of pre-clinical species such as mouse, rat and dog to help you identify the most appropriate in vivo model for your compound or explain unexpected differences in vivo results.

Our project timelines are short due to our regular supply of fresh kidney tissue. The robust data generated by our scientific experts will guide you in confidence for key decision-making steps.

An example of renal toxicity packages includes assessment of FDA-approved biomarkers (KIM-1, NGAL and clusterin) in our aProximate™ proximal tubule cell model. This kidney tissue model can be used to assess drug-induced cell health and monolayer integrity. Data can be acquired from three separate biological donor kidneys across multiple species.

Assay design
Basic Nephrotox Study Readouts
  • ATP
  • LDH
  • TEER
Comprehensive Nephrotox Study Readout
  • ATP
  • LDH
  • TEER
  • FDA-approved biomarkers for renal toxicity: Clusterin, NGAL and KIM-1
Add-on services
  • Inhibitor study
  • Cross-species comparison
  • Gene expression analysis
  • Cell lysate supply
  • Supernatant supply
  • RNA supply
Models

aProximate™ primary isolated kidney proximal tubule cells

Assay format

96-well Transwell® plates

Species
  • Human
  • Mouse
  • Rat
  • Dog
Assay overview
  • 3 compounds, 6 concentrations per compound
  • Time points: 0, 24h up to 3 days
  • Each data points performed in triplicates

Publication

Freshly isolated primary human proximal tubule cells as an in vitro model for the detection of renal tubular toxicity

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Example: In vitro nephrotoxicity screening Close Open

The aProximate™ model has been used in multiple studies including a collaborative drug safety evaluation study with Takeda Pharmaceuticals. The study used 36 compounds with known in vivo safety profiles (toxic or non-toxic) using aProximate™ PTCs as a training set. FDA-qualified kidney-specific biomarkers of kidney toxicity such as KIM-1, NGAL and clusterin were detected in the model, confirming its suitability to assess renal toxicity and evaluate renal drug safety during drug discovery. The model was then used to assess other compounds. It correctly classified four of six true positives and two of three true negatives, showing validation of model and the in vitro nephrotoxicity assay for detection of tubular toxicants. This work shows the potential application of quantifying translational biomarkers in freshly isolated aProximate™ PTCs for the assessment of nephrotoxicity within the drug discovery pipeline.

Renal toxicity graphs
High content comparison of two compounds for drug safety prediction using aProximate™ PTCs, indicating a possible nephrotoxic effect for compound B with increased levels of injury biomarkers and decrease of non-specific injury end points. Compound A is predicted as non-toxic.

Images

A microscope image of a nephron model
ZO-1 Immunocytochemistry staining of PTCs (red) and Hoechst nuclear staining.

Model for this service

aProximate™ proximal tubule cells

aProximate™ is one of the most advanced, near physiological, in vitro, kidney proximal tubule cell (PTCs) models. aProximate™ PTCs are derived from fresh human kidney tissue and grown on Transwells® where they remain well differentiated as a polarised cell layer forming tight junctions.

A microscope image of a nephron model
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