Renal Proximal Tubule Cell Monolayer Assay
| Service | Cell Line | Transporter | Technology | Membrane Type | Probe Substrate | Read Out | Reference Inhibitor | Positive Control | Dynamic Range |
|---|---|---|---|---|---|---|---|---|---|
| Renal Proximal Tubule Cell Monolayer Assay | Renal Proximal Tubule Cell Monolayer Assay |
Description
aProximate™: a sophisticated kidney proximal tubule cell platform
To gain a more detailed understanding of how new drugs may be transported and eliminated through the kidney and other organs in vivo and to mitigate the risk of renal toxicity in humans new drug molecules are tested in vivo in two preclinical species. However, these models are not always as predictive of human responses as expected. To address this problem, robust comparative in vitro models, such as the aProximate™ platform, are needed to improve in vitro-in vivo extrapolation (IVIVE).
aProximate™ is one of the most advanced near-physiological in vitro proximal tubule cell models. PTCs are isolated from fresh kidney samples and plated within 18 hours of tissue dissection. PTCs are grown on TranswellsTM filters where they remain well differentiated as a polarised cell layer that forms tight junctions (Figure 1). The aProximate™ proximal tubule monolayers are available from a number of species including, human, rat, dog, NHP and mouse.
Figure: aProximate™ proximal tubule cell model. Schematic diagram of aProximate™ PTCs showing the expression of all key renal transporters (left) and the formation of tight junctions as shown by ZO-1 tight junction protein labelling (bottom right). Diagram of transwell plates used to grown aProximate™: The PTCs grown on filters remain fully differentiated as a polarised cell layer (top right).
Unlike other primary and immortalized proximal tubule cells in culture aProximate™ PTCs retain expression of the relevant transporters involved in drug handling. Most transporters are expressed at an average of 30% compared to their expression in fresh kidney tissue (measured by transporter mRNA expression level). By contrast, immortalized kidney cell lines such as HK2, RPTEC and HEPTEC have very low or negligible transporter expression.
SOLVO offers tailored services using aProximate™ platforms in partnership with Newcells Biotech Ltd. These include:
- Identification of transporter-mediated renal drug clearance pathways for xenobiotics during drug development
- Identification of clinically important transporter-mediated Drug-Drug interactions during drug development and post market in clinic (drug induced AKI)
- Identification of cross species differences in renal drug handling - de risking adverse outcomes at first in man
- Application of renal model to identify renal target and target engagement/efficacy
- Development of screening regime for biologics transport and toxicity
- Identification of drug induced kidney damage using clinically relevant biomarkers of nephrotoxicity cross species as a predictive tool to improve first in man outcomes.
Learn more about the aProximate™ platform: Renal Proximal Tubule Cell Monolayer Technology.
You can find here our Webinar in collaboration with Newcells: Predictive cross-species proximal tubule cell models for drug development and safety assessment studies
Should you need any further information, please feel free to contact us!
