Glomerulus

Model formats

96 well Transwell® plates for podocyte renal toxicity service

Cell types

Podocytes
Multi-cell type model with endothelial and mesangial cells (coming soon)

Species

Human

Podocyte model for assessing glomerular toxicity and disease modelling

Newcells offers the first fully differentiated, primary podocyte model derived from kidney tissue for the in vitro assessment of drug-induced glomerular toxicity and disease modelling. The effect of a drug on the glomerular filtration barrier and podocyte glomerular permeability can now be easily evaluated in vitro.

Podocyte injury and proteinuria can be modelled in vitro at high throughput (96-well format) and assessed by measuring podocyte damage biomarkers, TEER and podocyte permeability.

Podocytes maintain the glomerular filtration barrier and similarly to proximal tubule cells, can be damaged by drugs. Drug-induced glomerular toxicity occurs progressively. First podocyte injury leads to cellular dedifferentiation causing perturbation of the podocyte monolayers architecture. This process in turn results in protein leakage as well as increased levels of protein in the urine, proteinuria, which can cause secondary renal tubular damage and chronic kidney disease (CKD).

Available analytical readouts

Permeability assay: performed with 70 kDa FITC-dextran
Cell viability: ATP and TEER measurements
Biomarker protein quantification
Inflammation: IκBα degradation, NF-κB translocation
ER stress and apoptosis: features of diabetic nephropathy
Fibrosis (Glomerulosclerosis): ECM deposition

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A microscope image of a convoluted tubules — Glomerulus surrounded by convoluted tubules (toluidine blue staining)

kidney tissue

Fully differentiated

Rapid results

Newcells Glomerulus Model

Accelerate your lead compound selection by understanding their mode of action in functional glomerular tissue

Recapitulate the function of the glomerular filtration barrier

Evaluate your compounds effect on glomerular toxicity

Derived from kidney tissue, expressing all podocyte markers

How to use our glomerular model?

Outsource your experiments to us

Take advantage of our expertise: with our fast and reliable glomerular toxicity service, we design the experiments with you to answer your questions and give you the results within 2 months. Our bespoke projects are carried out in our state-of-the-art UK facilities.

Contact an expert

Podocytes

Applications for podocyte model Close Open

Assessment of drug-induced glomerular toxicity
Evaluation of glomerular filtration barrier permeability
Disease modelling

Podocyte model characterisation Close Open

Newcells has developed the technology to generate a pure population of podocytes isolated from kidney tissue. Podocytes are highly specialised, terminally differentiated, epithelial cells with interdigitating foot processes connect by slit diaphragms which are rich in Nephrin, Podocin and CD2AP. Slit diaphragms are crucial to the selectivity of the filtration barrier, allowing filtration of water and smaller solutes but not large molecules. WT1 is a commonly used podocyte specific marker.

The podocytes are characterised by immunostaining of WT1, Nephrin, Podocin and CD2AP. High expression of these markers are maintained for >28 days.

Podocyte characterisation: immunostaining Isolated podocytes were immunostained for WT1, Nephrin, Podocin and CD2AP

Podocyte marker expression determined by high content imaging

Further characterisation has been validated using the markers Synaptopodin, Podocalyxin, Neph1 and ZO-1 (as a marker of tight junctions). Podocalyxin contributes to the charge barrier of glomerular filtration whereas Synaptopodin is expressed in differentiating podocytes when they develop the foot processes therefore Synaptopodin is considered to be a marker of mature podocyte phenotype.

Podocyte characterisation: immunostaining Isolated podocytes were immunostained for Synaptopodin, Podocalyxin, Neph1 and ZO-1

Isolated podocytes are grown in 96-well Transwell® plates until a monolayer is formed, recapitulating the function of the glomerular filtration barrier. The cellular monolayer demonstrates size selectivity comparable to in vivo as well as charge selectivity. As with all models developed at Newcells, the podocyte in vitro model is well-characterised and validated to supply clients with robust data.

Podocyte renal toxicity service Close Open

Newcells provides a custom service evaluating glomerular toxicity of drugs and toxins using our validated podocyte model.

With our regular supply of tissue, our projects timelines are short. The robust data generated by our scientific experts will guide you in confidence for key decision-making steps during drug development.

The standard service includes a set of assays to assess podocyte injury and podocyte permeability:

Trans-epithelial electrical resistance (TEER)
Permeability of 70 kDa FITC-dextran (increased podocyte permeability)
ATP cell viability

Evaluation of podocyte damage by Adriamycin, a chemotherapy drug known to induce glomerular toxicity. As expected, high concentrations of Adriamycin increase podocyte permeability and reduce podocyte viability. The decrease in TEER correlates with an increased FITC-dextran flux and a reduction in cell viability as measured by ATP release.

Additional assays will also shortly become available as part of an enhanced renal toxicity service including LDH cell health, IL-6 and MCP-1 protein quantification, caspase 3/7 assay and CHOP assay (Elevated CHOP levels correlate with ER stress-induced apoptosis).

Complete renal toxicity package: glomerulus and proximal tubule cells Close Open

Newcells offers a full in vitro renal toxicity evaluation by testing your compounds on both the podocyte model and aProximate™, the proximal tubule cell model. In vitro evaluation of both the glomerulus and proximal tubule damage will give a full assessment of the renal safety profile of your compound, significantly accelerating your drug safety studies. Species comparisons can be performed as well to determine the most suitable species for preclinical studies.