Cell4Pharma’s ciPTEC technology originates at the beginning of the 21st century. Researchers at the department of Pediatrics at the Radboud University Medical Center in Nijmegen, the Netherlands, were investigating the inherited disorder Nephropathic Cystinosis. Patients manifest before the age of 3 years with a deficient transporter capacity in the renal proximal tubule. To study this disease in the laboratory, Dr. Wilmer et al. cultured proximal tubule cells exfoliated in urine of patients, and, as control, of healthy donors. To establish sufficient study material, the primary tubule cells were immortalized via a technique proven to be successful in other cell types. The group lead by Prof. Dr. Van Den Heuvel and Prof. Dr. Levtchenko succeeded in their endeavors and ciPTEC was born.
Following the first characterizations demonstrating basic proximal tubule features such as CD13 and dpp-IV expression, they contacted Prof. Dr. Masereeuw and Prof Dr. Russel of the Department of Pharmacology and Toxicology. Their expert knowledge in renal drug transporter research was key in further characterizing the proximal tubule phenotype of the control ciPTEC derived from a healthy donor, including the demonstration of transporters. They provided antibodies to evaluate the expression of p-glycoprotein, MRP-4 and BCRP via Western blotting. When Wilmer showed the results few weeks later, the group concluded that ciPTEC was one of the first human renal cell lines, expressing drug transporters involved in renal elimination of drugs. The value of such a cell line during drug development at the pharma industry was immediately clear.
As post-doctoral researcher at the department of Pharmacology and Toxicology, Dr Wilmer further investigated the potential of ciPTEC for the pharma industry in 2010. To increase the use of ciPTEC in safer drug development, the stable introduction of functional OAT1 or OAT3 was a pivotal step forward. The group established a range of collaborations with pharma industry to establish cell-based assays to predict drug interactions and drug-induced toxicity. In collaboration with AstraZeneca, the functionality of OCT2 was demonstrated, as well the development of a multi-parametric high content screening assay in ciPTEC-OAT1 . Improved mechanistic insights could be provided for a lead compound leading to proteinuria using ciPTEC in a study in collaboration with Biomarin. On top, a kidney-on-a-chip model based on ciPTEC could be established in the NC3Rs NephroTube Challenge, in collaboration with Mimetas B.V. and FHNW, with support from Roche, Pfizer and GSK.
Supported by these collaborations and underscoring the wide potential of ciPTEC, Cell4Pharma B.V. was born in order to bring ciPTEC to all laboratories requiring a robust and highly predictive human renal cell line.
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