Kidney Disease Modelling - Newcells

Retinal platform

An in vitro, light responsive, retinal model for accurate predictions of in vivo outcomes you can have confidence in.

aProximateTM

Kidney platform

The most advanced near-physiological high throughput kidney proximal tubule cells (PTC) model to investigate drug transport modalities in vitro.

Lung epithelia model

Lung model

A model to investigate airway physiology, viral infection, drug safety and environmental impacts on lung airway epithelia.

Sinusoid iPSC-derived Liver model

Liver model

We are developing a model of liver sinusoid derived from human induced pluripotent stem cells (iPSC).

Kidney Disease Modelling

aProximate™ platform: The most advanced near-physiological high-throughput kidney proximal tubule cells (PTC) model providing mechanistic insights for kidney disease modelling.

Validated model: aProximate™ is a unique platform for Transporter, DDI, Nephrotoxicity Studies and Kidney Disease Modelling. Key renal transporters are expressed in proximal tubule cells model as well as kidney-specific biomarkers of injury upon challenge with xenobiotics. The use of such a reliable in vitro tool can help gain mechanistic insights into therapeutic targets and aid the development of novel treatments such as RNA therapeutics for both common and rare diseases.

Modelling molecular and cellular mechanisms of disease

The kidneys are essential organs playing a key role in homeostasis and maintaining the right balance between fluids, electrolytes, nutrients, and toxins. Renal dysfunction is either caused by external factors, such as drugs or toxins, or is linked to other underlying conditions affecting the pancreas and the heart, such as diabetes mellitus and cardiovascular disease. Rare inherited metabolic disorders also affect vital organs including the kidney. The kidneys ensure waste is excreted from the blood and nutrients are reabsorbed from the urine; a function performed by the kidney proximal tubule cells through a set of sophisticated transporters expressed both at the apical and basolateral cell membranes. When this equilibrium is perturbed, kidney function is affected.

To study renal dysfunction and perform in vitro kidney disease modelling, a robust model, such as such as aProximate™, expressing all the relevant transporters specialised in handling of drugs, solutes, and proteins is required. The platform is unique as it is highly predictive of in vivo outcomes. It also allows to gain insights into disease mechanisms and to assess therapeutic targets (e.g., renal transporters) of new drugs. aProximate™ has been used to study a range of diseases including chronic kidney disease, gout and metabolic disorders.

aProximate™, a reliable model to model common and rare kidney diseases.

Chronic Kidney Disease (CKD) – calcium and phosphate transport balance

CKD is defined as a change in kidney function or structure that affects the health of an individual for longer than 3 months irrespective of the cause. Early stages of CKD are asymptomatic, whilst end-stages are treated by dialysis and kidney transplant. The key cellular and molecular events causing CKD are an imbalance in the renin-angiotensin-aldosterone system, chronic inflammation, fibrosis, the presence of uremic toxins, and vascular calcification. Vascular calcification is not unique to CKD, but also seen in diabetes mellitus and cardiovascular disease, other factors associated to CKD. Vascular calcification occurs due to an imbalance in calcium and phosphate homeostasis, often as a result of a decrease in renal phosphate clearance. Renal sodium and phosphate co-transporters such as sodium-phosphate transporters type I and II (NaPi-I and NaPi-II) are therapeutic targets for CKD. These and other transporters are expressed in aProximate™, making it an ideal tool to model CKD in vitro by measuring the rate of intracellular accumulation of phosphate.

Metabolic disorders– renal tubular transport impairment

There is group of inherited diseases with inborn errors of metabolism where for example the transport of solutes such as salts and amino acids across the apical membrane of proximal tubule cells is affected. As a result, the reabsorption of essential amino acids is impaired leading to an excess of urinary excretion and amino acid loss from the body. The most frequent disorders are caused by mutations in solute carrier membrane transport proteins (e.g. SLC3, SLC6, SLC7, SLC15). This mutations are present metabolic disorders such as Iminoglycinuria, Cystinuria, Fanconi Syndrome, Nephrolithiasis, Hartnup disorder and Gitelman Syndrome.

aProximate™ PTCs express transporters of the SLC family (SLC3, SLC6, SLC7, SLC15) allowing the uptake of essential amino acids by PTC to be measured and modelled with this unique in vitro model. High throughput screening of drug modulating such amino acid transporters is also possible with the aProximate™ platform.

Gout – the uric acid transport

Uric acid is a waste product transported and eliminated by the kidney. When produced in excess, the kidneys are unable to excrete it fast enough and it accumulates in the blood (hyperuricaemia). This condition is known as gout and there is currently no effective clinical treatment for it. High levels of uric acid in the blood are the hallmark of gout, and sometimes also a sign of CKD. Urate transporters, such as NPT1, NPT4, OAT1, OAT2, OAT3, OAT4, URAT1, GLUT9, ABCG2 and PDZK1 have been shown to play a role in the upregulation of serum uric acid level, making them potential therapeutic targets for new treatments of gout. Targeting urate transporters and investigating urate-lowering drugs in vitro can provide insights into hyperuricaemia and related disorders.

With urate transporters expressed in the aProximate™ platform, in vitro high throughput analysis of inhibitors is straightforward. Given that aProximate™ is also highly predictive of in vivo outcomes, it is an ideal in vitro tool to understand uric acid transport and evaluate new treatments for gout.

State-of-the-art 2D and 3D cell-based assays

Newcells aProximate™ platform:
De-risk your drug discovery pipeline

Accelerate your research with a reliable and consistent supply of proximal tubule cells validated for drug safety & efficacy as well and drug transporter assays. The highly predictive platform provides detailed mechanistic insights into drug handling.  
Using in vitro aProximate™ platform accelerates and de-risk drug discovery and reduces the requirement for animal experiments for investigational studies of the kidney. 

aProximate™ The most advanced near-physiological high throughput kidney proximal tubule cell (PTC) model.

Recapitulates Proximal tubule physiology

  • Expression of all key renal transporters 
  • High throughput solution for industry 
  • Outperforms competitor in vitro models 
  • FDA approved kidney biomarkers 
  • Enables mitochondrial health monitoring 

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