Researchers we empower:
Cell4Pharma tackles your ADME-tox issues
based on our patented ciPTEC platforms:
ciPTEC is a human renal cell line that mimics the proximal tubule cells of the kidney. These cells are a main target for drug-induced kidney injury, caused by their role in highly efficient transport of drugs and toxic compounds from the bloodstream into urine. The most relevant drug transporter proteins involved in this process are stably and functionally expressed in our cell models.
ciPTEC
Functional Assays
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 successfully applied in our ciPTEC models: cell viability assessment (MTT, WST8, cell count), transporter activity (Pgp, BCRP, MRPs, OCT2, OAT1, OAT3), receptor-mediated endocytosis (megalin/cubilin), 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 production, O2 consumption, genetic modifications (CRISPR/Cas, baculo virus, lenti virus, retro virus), ROS production.
Extensive Validated Research
Cell4Pharma’s ciPTEC models are used in 30+ laboratories world-wide and used in 60+ peer-reviewed scientific publications. Moreover, the enormous amount of research has led towards a valuable basis that provided proof-of-concept to build upon further towards full validation to reduce renal adverse effect and replace animal experimentation in the future.
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 20 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.
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 include 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.
ciPTEC
Functional Assays
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 successfully applied in our ciPTEC models: cell viability assessment (MTT, WST8, cell count), transporter activity (Pgp, BCRP, MRPs, OCT2, OAT1, OAT3), receptor-mediated endocytosis (megalin/cubilin), 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 production, O2 consumption, genetic modifications (CRISPR/Cas, baculo virus, lenti virus, retro virus), ROS production.
Extensive Validated Research
Cell4Pharma’s ciPTEC models are used in 30+ laboratories world-wide and used in 60+ peer-reviewed scientific publications. Moreover, the enormous amount of research has led towards a valuable basis that provided proof-of-concept to build upon further towards full validation to reduce renal adverse effect and replace animal experimentation in the future.
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 20 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.
Drug Transporters
Cell4Pharma has developed a unique conditionally immortalised human proximal tubule epithelial 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 include 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.
ciPTEC 14.4 Primary Cells
CiPTEC 14.4 is a human conditionally immortalized proximal tubular epithelial cell line. Stably transfected by SV40T and hTERT, subcloned and well-characterized. Expressing proximal tubular markers alkaline phosphatase, di-peptidiyl peptidase IV and ZO-1. Maintained transport functionality for sodium-dependent phosphate reabsorption, megalin-cubilin receptor mediated endocytosis, organic cation transport (SLC22A2); p-glycoprotein (ABCB1), multidrug resistance protein 2/4 (MRP2/4), breast cancer resistance protein (ABCG2) and a range of metabolic enzymes.
ciPTEC OAT 1
Based on ciPTEC 14.4, including expression and functional uptake via organic anion transporter 1 (SLC22A6)
ciPTEC OAT 3
Based on ciPTEC 14.4, including expression and functional uptake via organic anion transporter 3 (SLC22A8)
ciPTEC 14.4, OAT 1, OAT 3
Robust data
The stable transfection and maintained epithelial characteristics lead to a cell line that will produce very robust data. Our validation studies demonstrated robust data for more than 20 passages.
Formation of 3D tubular structures
3D structure of a tubule with ciPTEC.
Intact drug transporter functionality
Using fluorescent probes specific for a transporter, we could demonstrate the functional expression of OCT2, P-glycoprotein, MRP4, BCRP and OAT1 (in ciPTEC-OAT1) and OAT3 (in ciPTEC-OAT3). The transport of fluorescent probes could be inhibited using specific inhibitors or competitors.
Used in 90+ peer-reviewed scientific publication
More than 10 years of research in world-wide academic and industry collaborations have lead to 90+ peer-reviewed scientific publications in the fields of pharmacology, nephrology, physiology and human pathology.
Proximal tubular epithelial characteristics
Extensive characterization demonstrated that ciPTEC in culture keeps its proximal tubular epithelial characteristics, such as specific transporter expression (OCT2, P-glycoprotein, MRP4, BCRP, NaPi2), gamma-glutamyl transferase expression, ZO-1 and CD13 expression, as well as the formation of cilia.
Conditionally immortalized
By viral transfection using SV40t antigen and hTERT, ciPTEC is proliferating at 33°C, while the SV40t antigen is absent upon culturing at 37°C, where ciPTEC proliferation is reduced.
Relevant drug transporter expression
Following characterization on a protein and gene level, we demonstrated specific transporter expression (OCT2, P-glycoprotein, MRP4, BCRP) in ciPTEC. Following stable transfection using vectors containing the human OAT1 and OAT3, we created ciPTEC-OAT1 and ciPTEC-OAT3 models.
Human origin
ciPTEC was originally derived from a human donor (female). The human origin results in the high predictivity for human renal adverse events and the versatile use of ciPTEC in the fields of pharmacology, nephrology, physiology and human pathology development of a semi-high throughput device in order to create a kidney on a chip.
Compatible with transient and stable transfections
Using different transfection techniques (retroviral, lipofectamine, lentiviral, CRISPR/Cas), we could introduce specific genes for a range of research purposes.
Biomarker expression upon toxicant exposure
In screening assays developed by Cell4Pharma, (non-)specific biomarkers for renal toxicity could be demonstrated upon toxicant exposure, including HO-1, miRNAs and LDH release.
Suitable for drug-drug interaction studies
The transport of specific fluorescent probes could be inhibited using specific inhibitors or competitors, which can also be used to study drug-drug-interactions.
Compatible with high throughput screening
Cell4Pharma’s ciPTEC can be cultured in 96 and 384 well plates. Together with it’s unlimited proliferation capacity allow high throughput screening.
Intact endocytic transport
Via receptor-mediated endocytosis, megalin and cubilin have an enormous capacity to reabsorb solutes from the glomerular filtrate. We demonstrated an intact endocytic apparatus.
Expression of renal drug metabolising enzymes
The human proximal tubular epithelium has a wide range of Phase I and Phase II metabolic enzymes of which a plethora was demonstrated to be expressed in ciPTEC.
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Testimonials
Because the cell line is robust in culture, the research leads to reliable results. As far as I am concerned, there is currently no kidney epithelial cell line available with an equally good predictive value for the human kidney.
The ciPTEC mimics primary renal cells, but you can culture them for a long time without losing their properties. The expression of transporters gives a more accurate response to drugs and toxins. The cells grow fast and are easy to handle.
ciPTEC is a well-accepted in vitro model to screen compounds for their DIKI potential.