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Our latest paper in collaboration with Pfizer on the role of OCT2/MATE in creatinine clearance is accepted in JPET.

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Proximal Tubule MPS Flow

Model formats

  • 96-well Transwells® (toxicity assays)

Cell types

  • aProximate™ - primary kidney proximal tubule cells


  • Human

Applying fluidic media flow and shear stress to freshly isolated kidney proximal tubule cells to improve phenotype and functional properties

Improved biological relevance and predictivity

By the simple adaption of our primary human proximal tubule cells grown in Transwells®, we have demonstrated that flow induces higher cilia expression and increased expression of a number of the key transporters, including large molecule transporters. Comparing the performance of cells under flow with those under static conditions, we have demonstrated increased sensitivity to known nephrotoxins. This approach has a wide range of applications to produce in vitro drug behaviour data in a micro-physiological system under flow with shear stress from a range of readouts such as protein biomarkers, cell viability and with the appropriate adaption high-content imaging.

aProximate™ MPS Flow features:

  • Freshly isolated cells from primary tissue which retain expression of all key markers and remain functional
  • Multi-well (96-well) design increases throughput capacity
  • Isolated flow in each well allows simultaneous testing of multiple conditions for rapid results
  • Adjustable flow using a rocking platform improves physiological relevance without the need of a pumping system
  • Ideal for drug developers requiring rapid access to MPS technology without the need to invest in specialised equipment

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High throughput

up to 96-well

Freshly isolated PTCs

under fluidic flow

Increased sensitivity

high transporter expression

aProximate™ MPS Flow Highlights

Accelerate your lead compound selection by understanding their mode of action in kidney tissue under flow


Fully differentiated and polarised kidney proximal tubule cells undergoing shear stress


Higher sensitivity due to increased expression of all key renal transporters


Higher predictivity of in vivo and clinical outcomes

Applications for aProximate™ MPS Flow Close Open

Kidney proximal tubule cells immunostained with ZO-1 following exposure to MPS flow

Proximal tubule cells under flow form a polarised monolayer showing defined and orderly expression of the epithelial tight junction ZO-1



Development of highly-differentiated human primary proximal tubule MPS model

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Why use Newcells aProximate™ MPS Flow model? Close Open

Limitations of current models

Many current renal in vitro models only have a limited ability to detect early indicators of nephrotoxicity. For example, immortalised cell lines or frozen primary proximal tubule cells (PTCs) do not retain physiologically relevant expression of key transporter proteins involved in drug handling resulting in models failing to be sufficiently sensitive to test compounds at clinically relevant concentrations. Other MPS systems, Organ-on-Chip and kidney-chip platforms have expanded in recent years to improve the predictability of preclinical studies. These systems are also limited in sensitivity due to the quality of the cells (immortalised or frozen PTCs), and the low number of cells in each chip. These MPS systems also tend to be low-throughput, restricting their use. To address these points, Newcells MPS Flow model has been developed in high-throughput formats and utilises freshly isolated PTCs which retain all key renal transporters and maintain functionality.

Relative expression of key renal transporters in aProximate MPS Flow system versus static model. There is increased expression across all transporters measured with significant upregulation particularly in OAT1, OAT3 and OCT2.

Increased Sensitivity

From an in vitro toxicological perspective, the upregulation of gene transcripts associated with key transporter proteins such as those that comprise the OAT and OCT families as well as endocytic transporters like Megalin and Cubilin is key to maintaining the primary cell phenotype and function of the PTC in culture after shear stress stimulation. This has been shown for aProximate™ MPS Flow in our functional toxicity with cells having undergone exposure to shear stress showing our MPS flow systems are even more representative of in vivo. Furthermore, due to the high surface area on the Transwell® inserts, a large number of PTCs are seeded, further increasing the sensitivity and allowing detection of  biomarkers such as NGAL, Clusterin and KIM-1.

Nephrotoxicity assay performed at day 10 by exposing cells to cisplatin for 72 hours. (a) TEER and (b) ATP release at day 10 in both static and flow conditions
Nephrotoxicity assay performed at day 10 by exposing cells to cisplatin for 72 hours. Renal stress biomarker release (KIM1, NGAL and Clusterin) at day 10.
aProximate™ MPS Flow description Close Open

For the aProximate™ MPS Flow model, cells are seeded on the basal side of the Transwell®, unlike the static model where the cells are seeded on the apical side.  The cells are then expanded to confluency in static culture before the inserts are placed into the microfluidic plate and media is added into the channel.

Proximal tubule cells are seeded on the basal side of the Transwell in our MPS Flow model to ensure cells are exposed to the fluidic flow and shear stresses from the media channels.

The MPS flow plate is then placed on a rocker platform tilting at a fixed frequency (0.1 cycles/min) allowing periodic, bi-directional, gravity-induced movement of media from one chamber to the other. This movement exposes the monolayer of cells to a continuous basolateral fluid shear stress that accurately mimics in vivo shear stress.


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