Technology

Cell4Pharma tackles your ADME-tox issues based upon our ciPTEC platforms: human renal proximal tubule epithelial cell lines stably expressing relevant renal drug transporters.

 

Functional assays and read-outs

Over the last decade, we have developed a range of cell-based assays, with limited inter-laboratory variations. Our experts will support a succesful technology transfer and are open to discuss your goals.

A selection of our assays that were succesfully applied in our ciPTEC models:

  • cell viability assessment (MTT, WST8, cell count)
  • transporter activity (Pgp, BCRP, MRPs, OCT2, OAT1, OAT3)
  • receptor-mediated endocytosis (megalin/cubulin)
  • metabolic enzyme function and expression (CYP, UGT, GST)
  • cytokine production
  • 3D microfluidic cultures
  • cilia expression
  • gene expression analysis
  • LDH release
  • NAG release
  • miRNA secretion
  • ATP production
  • lactate productoin
  • O2 consumption
  • genetic modifications (CRISPR/Cas, baculo virus, lenti virus, retro virus)
  • ROS production

ciPTEC: stably transfected

Our parent ciPTEC was immortalised using the temperature sensitive SV40ts A58 and human telomerase genes (hTERT) [Wilmer et al Cell Tissue Research 2010]. This technique resulted in a stable human cell line, with maintained tubular characteristics and transporter functionality for >60 passages. Further, the OAT1 and OAT3 expression models were achieved via Lenti viral transduction [Nieskens et al AAPSJ 2016]. All our cell lines are originally derived from urinary sediment from a healthy donor, who gave informed consent, without any history of renal or inherited disorders.

 

 

ciPTEC: plethora of drug transporters

Cell4Pharma has developed a unique conditionally immortalised human proximal tubule epitelial cell line (ciPTEC) expressing most relevant renal drug transporters endogenously. Our cells are protected under patent PCT/EP2010/066792.

To improve the plethora of stable drug transporter functionality in ciPTEC, our product portfolio was extended with ciPTEC-OAT1 and ciPTEC-OAT3 with a market introduction in 2017. As such, Cell4Pharma's ciPTEC platforms provide an excellent tool to predict pharmaco-kinetics, drug interactions and renal toxicity for potential pharmaceutical compounds.

Regulatory guidelines for drug elimination routes

The recent guidances for the pharmaceutical industry published by the Food and Drug Administration (FDA) in 2017 and the European Medicines Agency (EMA) in 2013 recommend that drug development should include identification of elimination routes via drug transport proteins and characterize drug-drug interactions (DDI). These inlude the investigation of renal drug transport studies at the sites of p-glycoprotein (Pgp), breast cancer resistance protein (BCRP), multidrug and toxin extrusion transport 1 and 2 (MATE1, MATE2-k), organic cation transporter 2 (OCT2) and organic anion transporter 1 and 3 (OAT1, OAT3). All transporters are present in our ciPTEC platforms.

Reduce drug-induced kidney injury

Extensive testing in collaboration with industrial clients since 2009 has resulted in obtaining proof of principle status for ciPTEC demonstrating high value for predicting DDI and renal toxicity at early stages of drug development. Simultaneous expression of most relevant drug transporters results in a unique cell system. As such, ciPTEC has the potential to decrease attrition during expensive clinical stages of drug development, by sifting out toxic compounds already during pre-clinical stages of drug development. Consequently, our technology will cut on the budget spent on drugs that never reach the market because of renal adverse effects. Using this background, we initiated compound screening with our cell-based assays as a service for medium and large pharmaceutical companies and provide our cell lines and protocols to our clients. Consulting our scientific experts will facilitate a succesfull technology transfer. 

 

 

Cell4Pharma's ciPTEC

Our human renal proximal tubule epithelial cell lines are now available for your research.