Cell4Pharma Joins the iGEM Mini Jamboree 2024 at TU Eindhoven : Celebrating Innovation in Synthetic Biology

On October 7th, 2024, Cell4Pharma had the privilege of joining an incredible lineup of sponsors at the iGEM Mini Jamboree, hosted by TU Eindhoven. This dynamic event brought together students, researchers, and industry professionals, all united by a shared passion for advancing synthetic biology. The day was filled with impressive presentations from student teams who are tackling global challenges with creativity and ingenuity.

As part of the sponsor community, we were thrilled to engage with these bright young minds and witness their innovative projects firsthand. From bioengineering solutions to environmental sustainability efforts, the range of ideas presented was truly remarkable. It was clear that these students are not just thinking about the future—they are actively shaping it.

Throughout the event, each sponsor had the opportunity to host a booth, and we were excited to meet so many enthusiastic participants. Students came by to ask questions, explore potential collaborations, and dive deeper into the work we do at Cell4Pharma. These interactions were a highlight of the day for us, offering valuable insights into how we can contribute to and learn from the next generation of scientists.

While we are proud to have supported this year’s iGEM Mini Jamboree, we were equally inspired by the collaborative spirit of the event. It was a fantastic opportunity to not only share our expertise but also to learn from the innovative ideas being developed by these talented students. The enthusiasm and dedication of everyone involved left a lasting impression on us.

We extend our heartfelt thanks to the iGEM teams who visited our booth and shared their projects with us. We look forward to seeing how their work will continue to evolve and hope to stay connected with this vibrant community. Cell4Pharma remains committed to supporting the future of synthetic biology and fostering innovation in the field.

Robust validated proximal tubule-on-a-chip

Drug-induced organ toxicity accounts for 30% of all drugs that fail prior to reaching the market. Within this, nephrotoxicity accounts for 2% of failures in the preclinical stages and 19% of all failures in Phase III. There is a significant translational gap between the preclinical models of nephrotoxicity and their predictive value through the clinical stages of drug development.

Renal proximal tubules are a major target for drug-induced kidney injury (DIKI) that needs evaluation during drug development. Two-dimensional in vitro proximal tubule epithelial cell (PTEC) models are often poor predictors of DIKI, because of the lack of physiological architecture and flow. The team at MIMETAS and Radboud University Medical Centre developed ‘NephroScreen‘ containing of polarized human proximal tubule cells in the OrganoPlate, as a better predictive in vitro system for drug-induced kidney toxicity (DIKI).

In this application note, we explain more about Nephroscreen and elaborate on why it’s an ideal model to study the potential toxicity of drugs and other substances involving active uptake via these transporters.

Learn more about:

1. A robust and validated 3D organ-on-a-chip proximal tubule
2. The wide range of compatible readouts, showing identification of nephrotoxicants in line with (pre)clinical compound profiles
3. Why it’s an ideal model to study the potential toxicity of drug substances involving active uptake via both organic anion and organic cation transporters

Want to learn more? Download the app note here.

Drug-disposition-on-a-chip: A European public private consortium to better predict the behaviour of drugs in humans by networked mini-organs.

We are excited to announce our involvement in the public-private consortium to develop a four organ on a chip model.

Organ-on-chip technology has allowed researchers to study physiological systems in vitro. Derived from human tissue, miniaturized organs allow for the precise study of the flow of (chemical) substances through specific organs. Now, a novel European consortium combines the expertise from leading research centres across public agencies, academia, and the pharma industry to take this technology to the next level. Initiated on January 1, 2021, this 4 year, 1.06 million EUR project, will aim to provide new scientific tools enabling better predictions of drug disposition in humans during drug development.

Drug development is a time consuming and expensive process considering that 7 out of 8 drugs in the pharmaceutical pipeline fail to reach the clinic. One big part contributing to this high failure rate is the limited translatability of efficacy and safety readouts from animals to humans. Absorption, Distribution, Metabolism and Excretion studies (ADME) determine the fate of a new drug in tissues and cellular systems of the body and are a cornerstone of this aforementioned translational assessment before entering the clinic.

Most of these ADME assessments are typically performed in animal models that can differ quite drastically to humans. A plethora of in vitro models, including micro physiological models based on human tissues or cells, have been developed with limited success. This is due to that fact that a simple static model (one without flow) based on a single organ or cell system does not accurately reflect the complex interactions between different organs involved in drug disposition.

To overcome these limitations, the consortium partners propose to develop a dynamic ‘drug disposition on-a-chip’ platform by combining and connecting the most relevant human organs associated with drug disposition, such as the intestine, the liver (including bile duct) and the kidney, through microfluidics and computational modeling. Together, these interconnected chips should cover the most important aspects of ADME, which are relevant for predicting a drug’s disposition behavior in humans, not only through better understanding of the absorption process, but also for understanding its efficacy and safety. In addition, this innovation could help to further reduce the use of animal models in preclinical research.

There are four main steps for implementation. First, the individual organ chips (liver, kidney, intestine, bile duct) need to be created by immobilizing the corresponding cells types. Second, these organ chips need to be interconnected with fluidic devices. In the third step, the functionality of the interconnected organ-on-a-chip devices need to be validated with sets of pharmaceutical drugs with known pharmacokinetic behaviour. Finally, verification is needed to show that the drug disposition in humans could be efficiently modelled with readouts from this newly developed system.

This consortium is a public-private partnership, with representation from regulatory agencies, academic institutions, small- and medium-sized enterprises, public organisations and pharmaceutical companies. The project is coordinated by Utrecht University (NL) and partners involved are: Novartis (CH), TNO, the Netherlands Organisation for Applied Scientific Research, (NL) and Cell4 Pharma (NL). The project is more-or-less equally funded by all partners through monetary contributions, scientific expertise and lab support, and co-funded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.

Upon successful development, the platform is expected to become an important tool for the characterization of ADME properties in the development process of new drugs. 

Webinar – How to predict drug-induced nephrotoxicity during drug discovery – AsraZeneca (ciPTEC)

How to predict drug-induced nephrotoxicity during drug discovery.

Cell4Pharma’s European Distribution Partners

We proudly present Cell4Pharma’s European distribution partners.

Bio-Connect (Benulux)

Clini Sciences (UK & Europe)

Labclinics (Spain & Portugal)

Tebu Bio (Europe)

Safety assessments for drug-induced kidney injury

Obtaining mechanistic insights on adverse effects in the kidney during clinical trials is challenging. 

We are going to show you how you can perform confident safety assessments on observed drug-induced kidney injury with our ciPTEC cell models. Just like we did with researchers at Biomarin, GSK, and AstraZeneca. 

As a researcher, it’s your job to understand adverse effects through mechanistic insights that allow you to determine the exact toxic potential, or to determine whether the risk is limited as compared to the benefits of the drug. 

It will be your results and insights that determine the course towards a successful market introduction.

Evaluating the risks

For example, the development of anti-sense oligonucleotides as therapeutic intervention for genetic diseases is associated with proximal tubular dysfunction and presented with proteinuria. 

This adverse effect was observed both in animal and clinical studies performed by BioMarin. Moreover, the effect seemed to be reversible when treatment was arrested and the toxicological importance was considered to be limited. 

Obviously, such observation demands further mechanistic investigations in order to fully understand the risks and pave the way for a confident and successful market introduction.

Getting answers

In case of the proximal tubule dysfunction as presented here, we’ll need to answer;

• Which mechanism is responsible for the reversible nature of the clinical proteinuria? and,… 
• Is the drug exposure leading to a relevant toxicological risk? 

The better you’re able to address these questions, the better your insights will be to determine the risks, and the bigger the impact your research will have. 

Therefore, arming yourself with a highly reliable and accurate renal cell model like ciPTEC is essential.

BioMarin results

ciPTEC was used by BioMarin to address these questions in the case of antisense oligonucleotide therapy in the treatment of Duchenne’s muscular dystrophy. 

Due to the high resemblance of ciPTEC with the in vivo situation and intact transporter capacity, we could demonstrate the uptake of the drug in ciPTEC. The drug competed with uptake of proteins that are normally taken up by the proximal tubule cells. 

This observation explained the mechanism behind the clinical observations: drug competition in the proximal tubule cells resulted in elevated levels of proteins ending up in the urine of treated animals and patients. 

Last but not least, our in vitro assays with drugs exposed to ciPTEC did not lead to a toxic response, underscoring the limited toxicological importance of the observations and so provided confidence to continue clinical studies towards market introduction. This study was published by Janssen MJ et al, Mol Ther Nucleic Acids 2019

ciPTEC is a valuable tool to help you understand the mechanism of toxicity observed in clinical trials and provide a platform to make an informed decision on the continuation of the drug development process.

If you would like to try ciPTEC yourself you can contact us: here. 

• Assay ready cryopreserved aliquots 
• Fully differentiated and pre-qualified
• For instant use, no cultivation required
• Improved reproducibility by homogeneous cell banks

If you have questions then please feel free to reply to this email. We are happy to help.

Coming up: Fail fast, without losing your next blockbuster

We’ll unpack that in our next blogpost. 

Martijn & Errol

Cell4Pharma

P.S.

If you would like to read more about the use of ciPTEC, here are three publications we think you’ll like:

• Publication: Sjögren AK et al. (2018)
• Publication:  Suter-Dick L et al. (2018)
• Publication: Vormann MK et al. (2021)
• If you still didn’t have enough; here is a library of 70+ publications you can check out.

We are excited to announce acCELLerate as our strategic partner. Together we are able to provide researchers with validated assay ready renal ciPTEC cells.

Interested in trying our ciPTEC cells? Send over an email to errol.byron@cell4pharma.com