Enhancing in vitro cardiotoxicity models with human iPSC technology

Enhancing in vitro cardiotoxicity models with human iPSC technology

Enhancing in vitro cardiotoxicity models with human iPSC technology

Enhancing in vitro cardiotoxicity models with human iPSC technology

With cardiotoxicity continuing to challenge drug discovery and rising rates of cardiac arrhythmias, advanced in vitro cardiac models are gaining momentum. In this article, we outline our work unlocking iPSC technology for cardiac safety researchers looking to build better models of cardiac disease and screening systems for cardiotoxicity.

Cardiotoxicity: a major challenge for drug discovery

Cardiotoxicity is responsible for one-third of pharmaceutical regulatory clearance failures, placing it amongst the biggest challenges in drug development[1]. To screen for this, a range of cardiotoxicity models have been used including animal models and primary cell models. While these models have added to our understanding, there is still a translational gap between the “bench” and the “clinic”, highlighting the need for more physiologically-relevant model systems that can better translate to humans[2].

This is where human induced pluripotent stem cells (iPSCs) hold great promise. Derived from the reprogramming of human donor material, iPSCs can be differentiated into cardiac cells and used to build in vitro models. And because they retain the donor characteristics (including disease mutations, complex ion channel activity and functional performance) they can offer a more human-relevant model for research and cardiotoxicity screening.  ​

Supporting cardiac research with high-quality iPSC-derived cardiomyocytes

At Axol Bioscience, we’ve been working with iPSCs in a quality-focused environment for over a decade and have developed a deep understanding of the challenges of this space. Our ISSCR-compliant quality management system drives consistency and quality in iPSC products manufactured at our ISO 9001-accredited production facility.

With the FDA Modernization Act 2.0 driving greater adoption of iPSC technology, we have engaged with the Health and Environmental Sciences Institute (HESI) and continue to support the growing in vitro cardiac and cardiotoxicity markets with our iPSC expertise and quality cell manufacturing.

axoCellsTM Ventricular Cardiomyocytes

As key components of in vitro cardiac and cardiotoxicity models, we have performed extensive characterization and functional assessment of our iPSC-derived ventricular cardiomyocytes, including electrophysiology and contractility assessments. Visit the dedicated page to explore the data.

axoCellsTM Atrial Cardiomyocytes

Atrial fibrillation is the most common worldwide arrhythmia, with rates expected to triple by 2050[3]. We have therefore developed high-quality, functional iPSC-derived atrial cells to support researchers looking to build in vitro arrhythmia models. Click the button below to explore the data:

We have also demonstrated distinct chamber-specific responses between our axoCells atrial and ventricular cardiomyocytes using the FLEXcyte 96 contractility system.

Supporting the industry with our NEW axoCells Atrial Cardiomyocyte kit

We recently announced the launch of our new axoCells™ Atrial Cardiomyocyte kit, an all-in-one bundle to unlock iPSC technology for in vitro arrhythmia and cardiotoxicity research.

Key features of our Atrial Cardiomyocyte kit are:

  • Tailored culture medium and optimized coating solution for growth of the cells
  • Demonstrate chamber-specific pharmacological responses (see below)
  • No evidence of endogenous arrhythmia
  • Developed for use in advanced in vitro atrial fibrillation and cardiotoxicity models

And with everything you need (including matched reagents) in one easy-to-use kit, you can save time and money, freeing you up to focus on the science and build better cardiac models for research and toxicity screening.

Click below to read more about the background to this product launch and further kit details.

Concepts on the horizon

We operate at the cutting edge of iPSC technology and are developing two exciting concepts to enhance in vitro cardiac research and cardiotoxicity screening:

  • Utilizing an innovative protocol developed at The Francis Crick Institute, we’re looking to produce highly pure populations of left ventricular cardiomyocytes for chamber-specific disease modeling and cardiotoxicity screening.
  • Alongside this, we’re working on a cardiac maturation media with the aim of enhancing cardiomyocyte maturity and boosting functional performance in cardiac models.

Download our 2024 Cardiac Guide to read more about these concepts, or contact us at operations@axolbio.com

We’ve produced a comprehensive overview of our in vitro cardiotoxicity and cardiac research offerings. Click below to download our 2024 Cardiac guide:


 

1 Francis Grafton, Jaclyn Ho, Sara Ranjbarvaziri, Farshad Farshidfar, Anastasiia Budan, Stephanie Steltzer, Mahnaz Maddah, Kevin E Loewke, Kristina Green, Snahel Patel, Tim Hoey, Mohammad Ali Mandegar (2021) Deep learning detects cardiotoxicity in a high-content screen with induced pluripotent stem cell-derived cardiomyocytes eLife 10:e68714 doi: https://doi.org/10.7554/eLife.68714

2 Pognan, F., Beilmann, M., Boonen, H.C.M. et al. The evolving role of investigative toxicology in the pharmaceutical industry. Nat Rev Drug Discov 22, 317–335 (2023). https://doi.org/10.1038/s41573-022-00633-x

3 Nesheiwat Z, Goyal A, Jagtap M. Atrial Fibrillation. [Updated 2023 Apr 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526072/

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