To produce powerful in vitro models of atrial-specific conditions, you need mature, functionally relevant atrial cardiomyocytes that behave as you’d expect. We recently published an application note comparing our axoCells atrial and ventricular cardiomyocytes across various functional and pharmacological parameters. In this article, we look at what this data means for drug discovery and- importantly- the millions of patients living with cardiac arrhythmias.
Atrial fibrillation is a global issue
Affecting over 37 million people worldwide, atrial fibrillation (AF) is the most common form of arrhythmia worldwide 1. As a major risk factor for stroke and cardiovascular disease, AF produces a significant global burden with a 1-year mortality rate around 25% 2.
Despite significant morbidity and mortality- and rising global prevalence- there have been significant translational challenges in the pursuit of better AF therapies 3. This has sparked great interest in new approaches to arrhythmia modelling, such as human iPSC-derived in vitro cardiac models.
axoCells atrial cardiomyocytes: functional and pharmacological relevance
Axol’s axoCells human iPSC-derived ventricular cardiomyocytes have been used extensively in research, drug development and cardiotoxicity testing due to their physiological and functional relevance. However, atrial-specific models (such as atrial fibrillation) need atrial cardiomyocytes specifically, due to the clear phenotypic and pharmacological differences between atrial and ventricular cardiomyocytes.
As described in the application note, we undertook an in-depth analysis of our axoCells atrial and ventircular cardiomyocytes, comparing their performance across a range of parameters on the FLEXcyte 96 platform.
This included:
- Contractility waveforms
- The effect of I(KACh) activation by Carbachol on beat rate and beat duration
- The inhibition of I(Kur) by 4-AP on beat rate and beat duration
Overall, our axoCells atrial cardiomyocytes produced distinct, expected pharmacological responses that validated them as a commercial resource for the in vitro modelling of atrial-specific disorders, such as atrial fibrillation.
Key takeaways
- Chamber specificity an important (although often neglected) factor in accurate cardiac modelling
- axoCells atrial cardiomyocytes produce distinct and expected pharmacological responses
- These cells can therefore be used as a powerful tool to perform in vitro drug screening and disease modelling on subtype-specific hiPSC-derived cardiomyocytes.
Download the full application note here: Contractility of axoCells atrial cardiomyocytes | AXOL Bioscience
- Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. International Journal of Stroke. 2021;16(2):217-221. doi:10.1177/1747493019897870
- Lee E, Choi EK, Han KD, Lee H, Choe WS, Lee SR, Cha MJ, Lim WH, Kim YJ, Oh S. Mortality and causes of death in patients with atrial fibrillation: A nationwide population-based study. PLoS One. 2018 Dec 26;13(12):e0209687. doi: 10.1371/journal.pone.0209687. PMID: 30586468; PMCID: PMC6306259.
- Heijman J, Guichard JB, Dobrev D, Nattel S. Translational Challenges in Atrial Fibrillation. Circ Res. 2018 Mar 2;122(5):752-773. doi: 10.1161/CIRCRESAHA.117.311081. PMID: 29496798.
